Hematology, Oncology, BMT Clinical Trials

AALL0932 Treatment of Patients with Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-lineage Lymphoblastic Lymphoma (B-LLy)

Purpose of Study:
This study is called a clinical trial. A clinical trial is a research study involving treatment of a disease in human patients. This study is organized by Children’s Oncology Group (COG). COG is an international research group that conducts clinical trials for children with cancer. More than 200 hospitals in North America, Australia, New Zealand, and Europe are members of COG.
 
How long is the study?
We would like to continue to follow your health status for about 10 years after you enter the study.

Who can participate:
Diagnosis
Patients must have newly diagnosed Standard Risk B-ALL or B-LLy Murphy Stages I or II.  Patients with Down syndrome are also eligible.

Age
Patients must be > 365 days and < 10 years of age (for B-ALL patients)
Patients must be >365 days and ≤ 30.99 years of age (for B-LLy patients)

What will happen during the study:
Treatment Plans
 
Induction – Part I
This study is being done in multiple parts.  The purpose of Induction is to collect information on leukemia and the effects of the treatment that will be given.  This will be given for 4 weeks.  The chemotherapy given during Induction is the current recommended treatment for Standard Risk (SR) B-ALL.  
 
Post Induction – Part II
In the remainder of therapy called post-Induction, we try to get rid of any remaining leukemia cells to keep the leukemia from coming back. This portion of therapy is broken up into 2 segments. The first more intense portion consists of Consolidation, Interim Maintenance (I & II) and Delayed Intensification. The last portion is called Maintenance. All stages of treatment are very important.
Part II is for the first more intense portion of therapy, which lasts approximately 7 months. A final consent describing Maintenance therapy will be discussed with you by your doctor prior to the beginning of Maintenance.

Who to contact:
Mark Ranalli, MD
614-722-3563
Mark.Ranalli@nationwidechildrens.org

A Phase II, open-label, single-arm, efficacy study of Tranexamic acid (TA) in the treatment of adolescent females with cyclic heavy menstrual bleeding (HMB)

Purpose of Study
The purpose of this study is to learn more about a drug called Tranexamic acid (TA), otherwise known as Lysteda.  We want to study how well Lysteda works in decreasing menstrual blood loss in young women and to see if parents and children participating in this trial think the drug is improving their quality of life.
 
Menorrhagia in young women with bleeding disorders is typically treated with a combination of treatments including surgery and hormonal contraceptives.  Some young women prefer not to use hormonal contraceptives due to concerns regarding compliance, possible long-term effects of hormones and the social implications of using a "birth control pill".  TA is a hormone-free medicine.

Tranexamic acid is taken orally during the first 5 days of menstrual bleeding.

Who can participate:
Lysteda has been approved by the Food and Drug Administration for use in patients > than 18 years of age but not for the age group that we will be looking at in this study.

For this study, we are looking for females to participate who are between 12-17 years old.  We hope to enroll 16 patients here at Nationwide Children's Hospital.

What will happen during the study:
This is an open-label study.  This means that each patient in the study will know what dose of study medicine (Tranexamic acid) she is being treated with.  The study staff will also know.  Your participation in this study will last for approximately 6 months.  If you agree to be in this study, we would ask you to do the following things:

• You will be asked to take the study medicine for 3 full menstrual cycles (Menses 2, 3 and 4). 
• The dose of study medicine will be 1.3 grams (2 tablets) taken three times daily.  This is taken each day for the first 5 days of your menstrual cycle. 
• Within 3 days of the end of each menstrual cycle (menses 2-4), you will receive a phone call from a member of the study team.  You will be asked questions about whether or not you have been taking the study medicine as prescribed by the study doctor.  You will also be asked questions on any adverse (unfavorable) events you may have experienced such as headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, dysmenorrhea (lack of period) and fatigue (feeling tired). 
• Also, within 3 days of the end of each menses, you will be asked to complete the surveys.

Who to contact:
Sarah O’Brien, MD
614-722-3250
Sarah.O'Brien@nationwidechildrens.org

ARST08P1 (Pilot 2) A Pilot Study to Evaluate Novel Agent Temozolomide in Combination with Intensive Multi-Agent Interval Compressed Therapy for Patients with High-Risk Rhabdomyosarcoma

Purpose of study:
The standard treatment for subjects with high risk rhabdomyosarcoma is surgery to remove the tumor (when possible), anti-cancer drugs (chemotherapy), and high energy x-rays (radiation therapy). The standard drugs used for rhabdomyosarcoma are vincristine, dactinomycin and cyclophosphamide, and are often called VAC therapy.

Current standard therapy does not work as well with tumors that have already spread at the time a subject is diagnosed. Past studies have been done using higher doses of cyclophosphamide but that has not increased the treatment success for high risk subjects. We chose the drug temozolomide because it has been shown to increase the effect of other anticancer drugs (chemotherapy) as well as high energy x-rays (radiation therapy). The combination of VAC and interval compression of Ifosfamide, etoposide, doxorubicin and irinotecan has been well-tolerated in children and adolescents with habdomyosarcoma, and other kinds of sarcomas.  

It is not known if adding temozolomide to high intensity chemotherapy will be helpful for high risk rhabdomyosarcoma, and it may increase the side effects of treatment.

The overall goals of this study:

• To find out the effects, good and/or bad, of giving high intensity chemotherapy containing temozolomide to subjects with high risk rhabdomyosarcoma or ectomesenchymoma.
• To see if early exposure to high intensity chemotherapy containing temozolomide will get rid of the cancer for as long as possible for high risk rhabdomyosarcoma subject.

Who can participate:
Age
<50 years of age at time of enrollment

Diagnosis
Patients with newly diagnosed, biopsy-proven metastatic rhabdomyosarcoma or ectomesenchymoma.
 
Additional screening for eligibility will be required.

What will happen during the study:
Treatment
The overall study has three different treatment plans, and each plan is called a 'Pilot'. Subjects are placed in a specific pilot based on when they enroll in the study. Currently, we are enrolling subjects in Pilot 2.
 
High intensity chemotherapy containing temozolomide that will be given on this study is experimental. It is not known how subjects with high risk rhabdomyosarcoma will do with this new approach to chemotherapy. It is not known if this combination (high intensity chemotherapy containing temozolomide) will get rid of the cancer for as long as possible.
 
Various methods will be used to give drugs:

PO - Drug is given by tablet or liquid swallowed through the mouth.
IV - Drug is given using a needle or tubing inserted into a vein. It can be given by IV push over several minutes or by infusion over minutes or hours.
SubQ - Drug is given by inserting a needle into the tissue just under the skin.
You will get some supportive care drugs to help with the effects of the chemotherapy. These drugs are commonly used with chemotherapy drugs. These drugs will be: Myeloid growth factors (for example, filgrastim) to help your blood counts recover from some of the chemotherapy drugs, Dexrazoxane, which helps protect your heart when you get doxorubicin, Mesna, which helps protect your bladder from bleeding when you get ifosfamide or cyclophosphamide. You will have additional tests and procedures during this study to assess your response to this treatment.
 
Timing
This study is expected to last 54 weeks. During this time, subjects in this clinical trial are expected to receive treatment on this pilot study for about 51 weeks. After treatment, subjects will have follow-up examinations and medical tests (3 weeks after the end of treatment and thereafter). We will continue to collect some medical information about how you are doing for 5 years after you start the study.

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ARST0921 A Randomized Phase II Trial of Bevacizumab (Avastin) and Temsirolimus (Torisel) in Patients with Recurrent/Refractory Rhabdomyosarcoma

Purpose of study:
We are testing 2 experimental drug combinations in the hope of finding a new therapy for fighting the type of cancer that you have. The 2 drug combinations are:

1. vinorelbine and cyclophosphamide with bevacizumab
2. vinorelbine and cyclophosphamide with temsirolimus

Bevacizumab and temsirolimus are experimental anticancer drugs that have not yet been approved by the Food and Drug Administration for use in treating rhabdomyosarcoma that is not responding to treatment or has come back after treatment.

Bevacizumab and temsirolimus work differently than the drugs vinorelbine and cyclophosphamide. As tumors grow, they need new blood vessels to grow with them in order to receive nutrients and survive. Bevacizumab works by blocking the growth of blood vessels, including blood vessels in tumors. Temsirolimus blocks a protein called mTOR. mTOR is involved in tumor growth, including the growth of blood vessels.

In laboratory studies, both bevacizumab and temsirolimus have been shown to work against some types of childhood cancers, including rhabdomyosarcoma. Each of the 2 drugs has been given to children with cancer. But they have not been given along with vinorelbine and cyclophosphamide to people with recurrent or refractory rhabdomyosarcoma.
 
The goals of this study are:

• To find out what effects (good and/or bad) bevacizumab, given with vinorelbine and cyclophosphamide, has on children and young adults with recurrent or refractory rhabdomyosarcoma
• To find out what effects (good and/or bad) temsirolimus, given with vinorelbine and cyclophosphamide, has on children and young adults with recurrent or refractory rhabdomyosarcoma
• To compare the effects of treatment with vinorelbine, cyclophosphamide and bevacizumab against the effects of treatment with vinorelbine, cyclophosphamide and temsirolimus

Who can participate:

• Patients must have had a previous histological verification of rhabdomyosarcoma at original diagnosis
• Patients with first relapse or progression of rhabdomyosarcoma are eligible
• Patients with primary refractory disease are eligible

Primary refractory disease is defined as first progression after receiving at least one course of cyclophosphamide or ifosfamide containing chemotherapy without prior demonstration of a radiographic response to chemotherapy (progression on irinotecan-containing chemotherapy without cyclophosphamide or ifosfamide containing chemotherapy will not be considered a first (progression).
Patient must be < 30 years of age at the time of study enrollment.
Additional screening for eligibility will be required.

What will happen during the study:
Treatment
The treatment involves cancer fighting medicine called chemotherapy. Treatment will be given in cycles that last 3 weeks (21 days). You will get 2 cycles of treatment and then there will be an evaluation. An evaluation means that you will have tests and imaging studies (scans) done to see if the tumor has changed. If the tumor has not gotten larger and you do not have bad side effects, your doctor may suggest you continue with treatment. If this happens, up to 10 more cycles of treatment may be given, for a total of up to 12 cycles. You will stop getting treatment on this study if the tumor gets larger or comes back, or if side effects from the treatment are too severe. If that happens, your doctor will discuss other treatment options with you.

Random Assignment
You will receive 1 of 2 different treatment plans. The treatment plan that you receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. You and your doctor will not pick which treatment you get. The randomization process is described in the COG Family Handbook for Children with Cancer.
 
Some subjects will be randomized to receive treatment on Arm A; others will be randomized to receive treatment on Arm B.
 
In this study you will get 1 of 2 treatment plans. The 2 treatment plans are the same except that some subjects will get the drug bevacizumab and some subjects will get the drug temsirolimus. The rest of the treatment with vinorelbine and cyclophosphamide will be the same.
 
The 2 treatment plans are called Arm A and Arm B as follows:
Arm A: vinorelbine and cyclophosphamide and bevacizumab (VC + B)
Arm B: vinorelbine and cyclophosphamide and temsirolimus (VC + T)

Timing
People in this clinical trial may get treatment on this study for up to 36 weeks. After treatment, you will have follow-up examinations and medical tests.

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ARST0531 Randomized Study for Patients with Intermediate-Risk Rhabdomyosarcoma (RMS)

Purpose of study:
The study doctors would like to see if adding an additional drug combination (vincristine plus irinotecan, or VI) is better than VAC alone. The standard time for radiation therapy to start for most patients with RMS is about 13 weeks after beginning chemotherapy. The study doctors will be looking at the effectiveness of giving radiation therapy earlier in the course of treatment (at 4 weeks instead of 13 weeks). Finally, the study doctors would like to see if a lower dose of cyclophosphamide is as good for treating RMS as the standard dose, but with less toxicity during treatment and afterwards (late effects).

The overall goals of this study are:

• To see if the new combination (VAC plus VI) is better than the standard chemotherapy (VAC) alone for treating intermediate risk RMS
• To compare the effects, good and/or bad, of a new combination (VAC plus VI) of chemotherapy
• To compare a new schedule (starting at Week 4) for giving radiation therapy to:
  • the standard schedule (starting at Week 13) for side effects (toxicity)
  • the older schedule (starting at Week 10) for effectiveness
  • to compare the side effects of a slightly lower dose of cyclophosphamide to the higher standard dose

Who can participate:
Patient must have Intermediate-risk RMS defined as:  

1. Embryonal, botryoid, or spindle cell RMS, or etomesenchymoma: Stage 2 or 3 and Group III
2. Alveolar RMS: Stage 1-3 and Group I-III

Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study.

Additional screening for eligibility will be required.

What will happen during the study:
Randomization
Subjects (people participating in the study) will get one of two different treatment plans. The treatment plan they get is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. You have an equal chance of being assigned to either treatment plan. A randomized study is the best way to find out if one treatment is better than another. That is why this study is planned the way it is.   

Treatment
Some participants will be randomized to get Regimen A (which is VAC alone) and some will be randomized to get Regimen B (which is VAC plus VI). Some subjects may also have more surgery if it becomes possible to remove more tumor. For all patients on both arms of this study, radiation therapy will start at Week 4.Evaluations (scans) to see how the tumor has changed will be done at Weeks 15, 30 and 43. If at any evaluation your tumor is larger, you will be taken off protocol therapy and you will discuss other treatment options with your doctor.
 
Timing
Treatment on this study will last for about 43 weeks. After you are done with treatment the Study Doctor will ask you to visit the office for follow-up exams every 2-4 months for four years and yearly for 5-10 years.

Who to contact:
Dr. Laura Martin, Principal Investigator
(614) 722-3583
Laura.Martin@NationwideChildrens.org
 

AEWS1031: A Phase III Randomized Trial for Initial Treatment of Non-metastatic Ewing Sarcoma

Purpose of study:
In this study, researchers want to find out if we can improve the treatment for your disease by adding another drug called topotecan to the 5 drugs used in standard treatment.  

We chose the drug topotecan because the combination of topotecan and cyclophosphamide has been found to be useful in treating some subjects with Ewing sarcoma when it has come back after treatment (recurrence). The combination of vincristine/topotecan/cyclophosphamide (VTC) has been well-tolerated in people with other types of sarcoma. A recent COG study added VTC to standard therapy for localized Ewing sarcoma and the early results indicate that VTC can be used in this way.
 
The overall goal of this study is:
To find if adding the drug combination VTC to the standard five-drug chemotherapy for Ewing sarcoma will get rid of the cancer better than the standard five-drug chemotherapy by itself. ?

Who can participate:
Diagnosis
Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing sarcoma or PNET of bone or soft tissue are eligible for this study.

No prior chemotherapy or radiation therapy is allowed. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection. Patients will still be eligible if unplanned excision was attempted or accomplished as long as adequate imaging was obtained prior to surgery.
 
Age
Patient must be < 30 years of age at the time of study enrollment.

Additional screening for eligibility will be required.

What will happen during the study:
Random Assignment
Subjects (people participating in the study) will receive 1 of 2 different treatment plans. The treatment plan they receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. The randomization process is described in the COG Family Handbook for Children with Cancer. You will be randomized to get either standard chemotherapy (Regimen A) or experimental chemotherapy (Regimen B). The randomization takes place at the time you are enrolled on the study. You have an equal chance of getting either one of the treatments.
 
Treatment
The treatment plan involves chemotherapy along with surgery and/or radiation therapy. The treatment on this clinical trial may take about 9 months. The treatment is divided into 3 stages: Induction, Local control and Consolidation therapy.  

Induction therapy is the use of chemotherapy to reduce/get rid of the cancer. The goal is to kill cancer cells and shrink the tumor so that the surgery/radiation therapy will be easier and safer.

Local control is treatment directly to the tumor, and will be surgery and/or radiation therapy.

Consolidation therapy is treatment intended to kill any remaining cancer cells so that the tumor is less likely to come back.

Each cycle of chemotherapy on this study will last 14 days. Induction will be 6 cycles of chemotherapy, and will last around 12 weeks. Local Control will begin upon recovery from Induction and may be surgery, radiation therapy, or both (as described below). That decision will be made by your doctors and will depend on the location and size of the tumor. Consolidation includes 11 cycles (22 weeks) of chemotherapy and may start during the period of Local Control. This means that sometimes radiation therapy and some chemotherapy will be given in the same weeks.
 
Local Control
If you are to have surgery only, this will happen after you recover from Induction therapy.
If you are to have radiation therapy only, it will likely be given during Weeks 1-7 of Consolidation.
If you are to have surgery first followed by radiation therapy, surgery will occur after you recover from Induction therapy. Radiation therapy will then begin after you recover from surgery.
If you are to have radiation therapy first followed by surgery, radiation therapy will be given during

Weeks 1-7 of consolidation and surgery will happen after radiation is completed.  The exact timing of chemotherapy and local control will depend on how well you recover from the drugs given during each cycle. You will also need time to heal from any surgery, and from the effects of radiation therapy.  

Timing
Subjects in this clinical trial are expected to receive treatment on this study for about 9 months. After treatment, subjects will have follow-up examinations and medical tests. We will continue to collect some medical information about how you are doing for 10 years from the time you start the study.
 
Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ARAR0332 Treatment of Adrenocortical Tumors with Surgery plus Lymph Node Dissection and Multiagent Chemotherapy

This type of tumor is called an adrenocortical tumor (ACT).

Treating ACT requires that the tumor be totally removed. Because of this, surgery is likely the most important part of standard treatment for ACT. The scale of the surgery will depend on the stage of the disease. Surgery often requires that some surrounding tissues and even parts of other organs be removed too.

ACT may return or spread to other parts of the body even after surgery. We think that some disease may remain in the lymph nodes nearby after the tumor has been removed. It is common for patients with early stages of ACT to have some of the lymph nodes near the tumor removed. We would like to remove all of the lymph nodes nearby for those subjects with an early stage of ACT who have a large tumor. We want to find out if this larger surgery than usual will offer a better cure rate.
 
If ACT is at an early stage and the tumor can be totally removed by surgery, then no other treatment is needed. However, for people with advanced disease, chemotherapy has to be used.
 
The drug mitotane is effective against ACT but at high doses it also causes many side effects. Most of our current information about the effects of this drug (both good and bad) has come from treatment on adults rather than children. Giving mitotane at lower doses in children may avoid some of the side effects and still help fight the tumor. When mitotane is given at a lower dose it needs to be taken for a longer period of time. It may have to be taken for several months for it to work.
 
Combinations of different chemotherapy drugs are used to treat cancers. Recent studies have shown that adding the drug mitotane to a combination of the drugs cisplatin, etoposide and doxorubicin can be effective. By giving mitotane with other drugs, instead of alone, we may improve the treatment for ACT.
 
The main goals of this study are:

1. To see how effective surgery alone is for subjects with early stages of ACT (Treatment Groups 1 and 2).
2. To find out if it is better to do a larger surgery than usual (and remove more lymph nodes) in some subjects (Treatment Group 2).
3. To find out how well a combination of mitotane with cisplatin, etoposide and doxorubicin works for subjects with more advanced stages of ACT (Treatment Group 3).

The other goals of this study are:

1. We want to make sure that the benefits of larger surgery is better for some early stage of disease. We want to make sure that the benefits outweigh the added risks;
2. To find out how common it is for lymph nodes to be affected by ACT;
3. To find out what the risks (toxicities) of mitotane are when it iscombined with certain other chemotherapy drugs.?  

Who can participate:
Newly diagnosed patients with histological diagnosis of adrenocortical carcinoma. Patients must be less than 22 years of age at the time of diagnosis.

Additional screening for eligibility will be required.

What will happen during the study:

Treatment  
You will get chemotherapy, and if there is a good response you may have another surgery. Surgery will include removing the tumor and also all of the lymph nodes nearby.  If the cancer has spread, then any other tumors in other parts of the body will also be removed, when possible.

The chemotherapy will last about 8 months (32 weeks). If you also have surgery then the total treatment time may be longer.
If you choose not to take part in this study you will likely still get the same chemotherapy drugs and similar surgery.
 
Chemotherapy Schedule
You will get Induction therapy over a period of 6 to 12 weeks in order to shrink the tumor. You might then have another surgery.  If the tumor shows a good response to Induction therapy, then you will go on to Continuation therapy. Continuation therapy will last about 20 to 26 weeks.Induction therapy is the use of chemotherapy to reduce/get rid of the cancer. If the cancer goes away then the disease will be “in remission”. Continuation therapy is treatment intended to make the cancer stay in remission.
 
Induction Therapy
Induction therapy consists of 2 to 4 cycles of chemotherapy with the drugs mitotane, cisplatin, etoposide and doxorubicin. Each cycle will last 21 days. After 2 cycles you will be evaluated and if surgery is right for you it will be scheduled as soon as possible. 

Continuation Therapy
You will have 4 to 6 more cycles of chemotherapy with the same drugs used during Induction. The drugs will be given in the same way. Once you have finished a total of 8 cycles of chemotherapy, you will continue to get mitotane alone every day, for up to 8 more weeks. The total time that you will get mitotane will be 8 months.

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ACNS0332 Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients  

Purpose of study:
The overall goal of this study is to compare the effects, good and/or bad, of the chemotherapy drugs carboplatin and isotretinoin on subjects with high risk medulloblastoma and to find out if one or both are better than standard therapy alone.  
 
In this study you will get either standard therapy alone, standard therapy plus one of the chemotherapy drugs added to the regimen, or standard therapy plus both of the chemotherapy drugs.
 
The main aims of this study are:

• To find out if giving the drug carboplatin along with radiation therapy is more effective than giving radiation therapy alone.
• To find out if the drug isotretinoin can improve the survival of subjects with high risk medulloblastoma.

Other aims of this study are:

• To measure any effects that the different types of treatment have on the subject’s quality of life (general well-being).
• To measure the brain function of subjects (measuring intelligence, memory, language, nonverbal skills, attention, and academic achievement) and to examine the relationship between the subject’s level of brain function and their quality of life.

Who can participate:
Newly diagnosed, previously untreated: (1) M0 Medulloblastoma with >1.5 cm2 residual; (2) M+ Medulloblastoma; (3) M0 or M+ Supratentorial PNET (including pineoblastoma).

Patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor.

Additional screening for eligibility will be required.

What will happen during the study:

Random Assignment
Subjects (people participating in the study) will receive 1 of 4 different treatment plans. The treatment plan they receive is decided by a process called randomization.  Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. Subjects who have had clinical depression or an allergy to parabens or soybeans will be randomized to Regimen A or Regimen B and will not receive isotretinoin.
 
Treatment Plan
The treatment plan will begin within 31 days after your surgery (to remove the tumor) and will involve a combination of radiation therapy and chemotherapy.  The treatment on this clinical trial takes either 9 or 15 months (depending on the treatment arm you are randomized to) and is divided into 2 or 3 stages (also depending on the treatment arm you are randomized to).  
 
The first stage of therapy is called chemoradiotherapy.  All subjects will receive a combination of radiation therapy and chemotherapy to kill the cancer cells left over after surgery.  This stage of therapy will take 6 weeks.  Some subjects will have an extra chemotherapy drug, carboplatin, added to this treatment phase.   
 
In the second stage of therapy, called Maintenance, all subjects will receive a combination of chemotherapy drugs (see Attachment #1 for a list of drugs used).  Maintenance therapy will last 6 months. The goal of maintenance therapy is to kill any remaining cancer cells that are left over from chemoradiotherapy.  Some subjects will have an extra chemotherapy drug, isotretinoin, added to their regimen of chemotherapy drugs during this stage.  
 
Only some subjects will go onto a third stage of therapy, called Continuation.  Continuation therapy will consist of 6 more months of therapy with the drug isotretinoin.  
 
The stages of therapy and chemotherapy drugs that you receive will depend upon which treatment arm you are assigned to.  You will be "randomized" into one of the study groups described below. All subjects will receive the standard therapy for medulloblastoma, but some subjects will receive additional drugs during their course of therapy.  
 
The four treatment arms are as follows:

• Arm A:  will receive standard chemoradiotherapy (radiation therapy and the drug vincristine).   Subjects will then receive standard Maintenance chemotherapy.
• Arm B:  will receive chemoradiotherapy plus the experimental drug carboplatin.  Subjects will then receive standard Maintenance chemotherapy.
• Arm C:  will receive standard chemoradiotherapy.  Subjects will then receive Maintenance therapy with the addition of the drug isotretinoin and Continuation therapy with isotretinoin.
• Arm D: will receive chemoradiotherapy plus the experimental drug carboplatin.  Subjects will then receive Maintenance therapy with the addition of the drug isotretinoin and Continuation therapy with isotretinoin. 

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ACNS0334 A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children< 36 Months Old

Purpose of study:
The purpose of this study is to compare two experimental treatment regimens to see if one is better for subjects with high risk medulloblastoma or primitive neuroectodermal tumor (PNET).  Each regimen consists of induction, consolidation, and blood stem cell rescue.

The difference in the regimens is that in one regimen an additional drug, methotrexate, will be added to the induction therapy.  We would like to know if adding methotrexate will prove more effective than not adding methotrexate during induction therapy.  We do not know if adding methotrexate will prove more effective and it may cause additional side effects.

The overall goal of this study is to compare the effects, good and/or bad of induction therapy that includes methotrexate with induction therapy that does not include methotrexate on infants with high-risk medulloblastoma/PNET to find out which is better.In this study, you will get either induction with methotrexate or induction without methotrexate. You will not get both.

Other goals of this study are:

1. To see how the study treatments affect the quality of life of subjects (people participating in the study)
2. To see how the study treatments affect the brain development of subjects
3. To look at tumor tissue to see if there are differences in tumors that can help scientists learn more about high-risk medulloblastoma/PNET and ways to treat it.?

Who can participate:
Children less than 36 months (3 years) of age at time of definitive surgery who have high risk Medulloblastoma will be eligible for study entry.  

Additional screening for eligibility will be required.
 
What will happen during the study:
Randomization
Subjects (people participating in the study) will receive 1 of 2 different treatment plans. The  treatment plans are called Regimen A and Regimen B. The treatment plan you receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. The randomization process is described in the COG Family Handbook for Children with Cancer.

Some subjects will be randomized to receive Regimen A induction; others will get Regimen B induction. The rest of the study treatment (surgery and consolidation with stem cell rescue) will be the same in both groups of subjects.

Treatment Plan
The treatment on this clinical trial takes about 6 months. It is divided into 3 stages: induction and consolidation with stem cell rescue. Subjects may also have a second surgery between induction and consolidation. Subjects will receive a total of 6 cycles of chemotherapy – 3 cycles during induction therapy and 3 cycles during consolidation therapy. Each cycle of Induction chemotherapy lasts about 21 days and Consolidation chemotherapy about 28 days.

Chemotherapy during Consolidation is given in three 28 day cycles. Your stem cells will be given after each cycle to help the bone marrow recover more quickly.  

The 2 different treatment plans are the same except for the drugs given during induction.  

Regimen A
You will get 3 cycles of induction therapy with common chemotherapy drugs. During this time, your blood stem cells will be collected and stored for use later in your therapy.

If the tumor goes away with the induction therapy, you will then have 3 cycles of consolidation therapy with 2 other drugs. With each cycle of consolidation when the drugs are done, some of your blood stem cells will be given back to you. This is called stem cell rescue.

If the tumor has gotten smaller but is not completely gone or does not change in size after induction therapy, you may have a second surgery to try to remove the rest of the tumor. After surgery, you will then have 3 cycles of consolidation therapy . With each cycle of consolidation when the drugs are done, some of your blood stem cells will be given back to you (stem cell rescue).

Regimen B
You will have 3 cycles of induction therapy with the same drugs used in Regimen A plus  the addition of  one other drug. The rest of the therapy is the same as on Regimen A.  
 
Timing
Subjects will receive a total of 6 cycles of chemotherapy – 3 cycles during induction therapy and 3 cycles during consolidation therapy. Each cycle of Induction chemotherapy lasts about 21 days and Consolidation chemotherapy about 28 days.?
 
Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ACNS0831 Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients with Newly Diagnosed Ependymoma Ages 1 to 21 years

Purpose of study:
Recent studies of young children have shown that chemotherapy (anti-cancer drug therapy) can help shrink or get rid of ependymoma tumors. Other studies have shown that some children (about 15%) who received chemotherapy before radiation therapy had their tumors grow while receiving the chemotherapy. For this reason, study doctors think that if people with ependymoma are to receive chemotherapy before radiation therapy, the chemotherapy should not last a long time. This is called a short course of chemotherapy.

Since your tumor was partially removed by surgery, you will receive induction chemotherapy while on this study and, depending on your response to the induction chemotherapy, one or more of the following: a second surgery, radiation therapy, maintenance chemotherapy, and/or observation.
 
The overall goals of this part of the study are:
For patients whose tumor was partially removed by surgery, to see if treatment with a short course of chemotherapy can:

1. kill any remaining tumor, or
2. increase the number of patients whose remaining tumor can be completely removed by a second surgery.

Other goals of this study are to:

1. Study the effects of surgery, radiation therapy and chemotherapy on learning, thinking, hearing and the production of hormones (substances made in the brain that affect growth and development).
2. Study tumor tissue and blood for possible genetic and biologic factors related to ependymoma.

Who can participate:
Patients must be greater than 12 months of age and less than 21 years of age at the time of study enrollment.

Patients must be newly diagnosed with intracranial ependymoma. Patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above.

The diagnosis of intracranial ependymoma must be histologically confirmed.

Additional screening for eligibility will be required.

What will happen during the study:
Treatment
All subjects will begin with a short course of chemotherapy, called Induction chemotherapy, which will start 2 weeks after entering the study. The chemotherapy will be given over 7 weeks. You will be evaluated (have scans) after the completion of Induction chemotherapy. What happens next is determined by the features of your tumor and how your tumor reacted to Induction chemotherapy.

If the tumor has spread into other areas of the brain (metastasized), you will be taken off this study, and your doctors will talk to you about other treatment options.

If the tumor has completely gone away after Induction chemotherapy, the tumor was located in the upper part of your brain and the tumor cells are favorable, you will have no further treatment and will be carefully watched (Observation).

If the tumor has completely gone away after Induction chemotherapy, but the tumor was not located in the upper part of your brain and/or the tumor cells are unfavorable, you will have more treatment. You will be randomized to receive either radiation therapy and more chemotherapy (Maintenance) or to receive radiation therapy and then be carefully watched (Observation).

Timing   
Induction chemotherapy consists of 2 cycles and lasts for a total of about 7 weeks (or about 49 days). Cycle A lasts 3 weeks (21 days) and Cycle B lasts 4 weeks (28 days). All subjects will receive Induction chemotherapy.

Not all subjects will receive Maintenance chemotherapy. If you do receive Maintenance chemotherapy, it will be given after radiation therapy. Maintenance chemotherapy lasts for a total of about 12 weeks (or 84 days).

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

ACNS0821 Randomized Phase II Screening Trial for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood

Purpose of study:
This new study uses the results of these earlier studies, and looks at how well giving temozolomide and irinotecan daily for 5 days every 28 days works when given to children and young adults with recurrent or refractory medulloblastoma/PNET.

Although we think that this new treatment might be able to improve or slow the growth of recurrent or refractory medulloblastoma/PNET for some people, we would like to find out if adding another drug to the combination will help more people. In this study, we will add the experimental drug bevacizumab for half of the people that participate in this study.  
 
Bevacizumab works differently than the chemotherapy drugs temozolomide and irinotecan. As tumors grow, they need new blood vessels to grow with them in order to receive nutrients and survive. This blood vessel growth is called angiogenesis. Bevacizumab is an angiogenesis inhibitor. That means bevacizumab works by blocking the growth of blood vessels, including blood vessels in tumors. Adding bevacizumab to treatment with temozolomide and irinotecan is experimental.
 
The overall goals of this study are to:

1. Find out what effects, good and/or bad, giving temozolomide together with irinotecan daily for 5 days every 28 days has on people with recurrent or refractory medulloblastoma/PNET.
2. Find out what effects, good and/or bad, adding bevacizumab to treatment with temozolomide and irinotecan has on people with recurrent or refractory medulloblastoma/PNET.

Who can participate:

Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy.
 
Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence.
 
Additional screening for eligibility will be required.
 
What will happen during the study:
Randomization
Subjects (people participating in the study) will receive one of two different treatment plans. The treatment plan they receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study. Some subjects will be randomized to receive treatment on Arm A; others will be randomized to receive treatment on Arm B.
 
Treatment Plan
Treatment will be given in cycles that last 4 weeks (or 28 days) each. You will get 2 cycles of treatment and then there will be an evaluation. Evaluation means that you will have imaging studies (scans) done to see if the tumor has changed. If the tumor has not gotten larger and you do not have bad side effects, you will continue with 2 more cycles of treatment. Then you will have another evaluation of your tumor. After the fourth cycle, your doctor may suggest you continue with treatment if your tumor is shrinking or staying the same size and you do not have bad side effects. If this happens, up to 8 more cycles of treatment may be given, for a total of 12 possible cycles.
 
The two different treatment plans are the same except for the drug bevacizumab.
 
The two treatment arms are called Arm A and Arm B as follows:

• Arm A: (TEMO+IRIN) - Treatment with temozolomide and irinotecan
• Arm B: (TEMO+IRIN+BEVA) - Treatment with temozolomide and irinotecan and bevacizumab

Who to contact:
Mark Ranalli, MD, Principal Investigator
614-722-3563
Mark.Ranalli@NationwideChildrens.org
 

ACNS0822 A Randomized Phase II/III Study of Children with Newly Diagnosed High-Grade Gliomas 

Purpose of study:
This study is being done in 3 parts. In Part 1 of this study we found the dose of vorinostat that can be given safely to subjects during radiation therapy. This dose will now be used in this part of the study, Part 2. Part 2 of this study will test and compare 3 treatments.

Part 3 of this study will compare the 2 best treatments from Part 2. People who are in Part 2 of this study will not be in Part 3. We are now doing Part 2 of the study. You are being asked to enroll on Part 2 of this study.
 
The goals of Part 2 of this study are to:
Find out what effects, good and/or bad, chemoradiotherapy with vorinostat followed by maintenance therapy with bevacizumab and temozolomide has on people with newly diagnosed high-grade gliomas. The combination of vorinostat with radiation therapy is experimental.  Maintenance therapy with bevacizumab and temozolomide is experimental.

Find out what effects, good and/or bad, chemoradiotherapy with bevacizumab followed by maintenance therapy with bevacizumab and temozolomide has on people with newly diagnosed high-grade gliomas. The combination of bevacizumab with radiation therapy is experimental.  Maintenance therapy with bevacizumab and temozolomide is experimental.

Find out what effects, good and/or bad, chemoradiotherapy with temozolomide followed by maintenance therapy with bevacizumab and temozolomide has on people with newly diagnosed high-grade gliomas. The combination of temozolomide with radiation therapy is not experimental.  Maintenance therapy with bevacizumab and temozolomide is experimental.

Compare the effects of the three treatments above to find out which is better at getting rid of or shrinking tumors and has the least amount of side effects.

The goals of Part 3 of this study are to:

Compare the effects of two treatments to find out which is better at getting rid of or shrinking tumors and has the least amount of side effects. The two treatments are:

• Chemoradiotherapy with [insert either bevacizumab or vorinostat] followed by maintenance therapy with bevacizumab and temozolomide has on people with newly diagnosed high-grade gliomas. The combination of [insert either bevacizumab or vorinostat] with radiation therapy is experimental.  Maintenance therapy with bevacizumab and temozolomide is experimental.
• Chemoradiotherapy with temozolomide followed by maintenance therapy with bevacizumab and temozolomide has on people with newly diagnosed high-grade gliomas. The combination of temozolomide with radiation therapy is not experimental.  Maintenance therapy with bevacizumab and temozolomide is experimental.

Who can participate:
Patients must be greater than or equal to 3 years and less than 22 years at the time of enrollment.

Patients must have a newly diagnosed high-grade glioma such as: anaplastic astrocytoma, glioblastoma multiforme,or gliosarcoma. Patients with primary spinal cord malignant gliomas are eligible. Patients with primary brainstem tumors are not eligible. Patients with a diagnosis of oligodendroglioma or oligoastrocytoma are NOT eligible.

Additional screening for eligibility will be required

What will happen during the study:
Random Assignment
Subjects (people participating in the study) will receive one of 3 different treatment plans. The treatment plan they receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer to make sure that there are about the same number of people on each treatment plan of the study.

Randomization
Subjects will be randomized to either Arm A with vorinostat, Arm B with temozolomide, or Arm C with bevacizumab. The radiation therapy itself will be the same in all groups of subjects. Maintenance therapy will also be the same in all groups of subjects.
 
Treatment Plan
The treatment plans involve cancer fighting medicine called chemotherapy and radiation therapy. The treatment on this clinical trial takes about 12 to 14 months. It is divided into 2 phases.
 
The first phase of treatment is called “chemoradiotherapy”. This phase lasts about 70 days, or 10 weeks. During this first phase, you will be given radiation therapy to the brain 5 days a week for 6 weeks. Within the first week of starting radiation therapy, you will begin taking one of 3 drugs (bevacizumab, vorinostat, or temozolomide) during this phase. You will continue taking the drug while you receive radiation therapy. After you complete radiation therapy and the treatment with the drug, you will have a 4-week rest, during which no treatment is given.
 
The second phase of treatment, called Maintenance therapy, begins after the 4-week rest period. During Maintenance therapy, you will not receive any further radiation therapy but you will have more chemotherapy. Maintenance therapy consists of 1 cycle of chemotherapy treatment repeated for up to a total of 12 cycles. Each cycle is 28 days long. During each cycle, you will receive two drugs, called bevacizumab and temozolomide. Temozolomide will be given on 5 days and bevacizumab will be given on 2 days during each cycle.  Maintenance therapy lasts about 336 days or 11 months.
 
The 3 treatment plans are the same except for a difference in what drug you will receive during chemoradiotherapy. All treatment plans will use the same radiation therapy. All treatment plans will use the same Maintenance chemotherapy.
 
Timing
The treatment plans involve cancer fighting medicine called chemotherapy and radiation therapy. The treatment on this clinical trial takes about 12 to 14 months. It is divided into 2 phases:

1. The first phase of treatment is called “chemoradiotherapy”. This phase lasts about 70 days, or 10 weeks.
2. The second phase is Maintenance therapy, and this phase lasts about 336 days or 11 months

 
Who to contact:
Dr. Laura Martin, Principal Investigator
(614) 722-3583
Laura.Martin@NationwideChildrens.org
 

COG AALL1131 A Phase III Randomized Trial for Newly Diagnosed High Risk B-precursor Acute Lymphoblastic Leukemia (ALL) and testing Clofarabine in the Very High Risk Stratum. (Non-Down syndrome and Down syndrome)

Purpose of study:
(Non-Down Syndrome: HR-ALL or VHR-ALL)
Induction
In the initial stage of treatment for ALL, called Induction, we try to remove all visible signs of leukemia and allow normal blood cells to be restored. This is called remission. The cancer fighting medicine (chemotherapy) given during Induction on this study is one of the current standard Induction treatments for HR-ALL (High Risk B-precursor Acute Lymphoblastic Leukemia). Five chemotherapy drugs are used during this part of treatment.  

The purpose of this part of the study is to collect information about your leukemia that will be used to guide further therapy and to understand effects of Induction therapy on you. Information gathered on the AALL08B1 will be used to help further define your risk group and guide further therapy. (AALL08B1 is a biology study, required prior to the theraputic study AALL1131). Your doctor will know your final risk group by the end of Induction. You will be offered the chance to continue treatment on other parts of this study once your final ALL risk group is known.
 
The overall goal of this study is to collect information about your leukemia and about the effects of the first phase of treatment, called Induction.
 
Post Induction
Even though treatment success rates are very good for people with HR-ALL, some patients still have relapse of their leukemia. Therapy on this study attempts to decrease the number of people who relapse in the central nervous system. This is called CNS relapse.
 
The CNS is made up of the brain and spinal cord and the fluid that surrounds them. One of the ways doctors try to prevent CNS relapse is by giving some of the chemotherapy into the fluid surrounding the spine. Medicines given into the spinal fluid are given intrathecally or IT. This study looks at how well CNS relapse can be prevented in children with HR-ALL by comparing the use of 3 drugs (methotrexate, hydrocortisone, and cytosine arabinoside) given intrathecally. This is called triple intrathecal therapy or ITT. We will compare ITT to the standard use of 1 drug (methotrexate) given intrathecally (IT MTX). The use of ITT is experimental on this study. However, ITT has been given to many people will ALL and has been well tolerated. We do not know which approach is better. That is why we are doing this study.
 
This study also includes studies that aim to better understand the things that contribute to side effects of cancer treatment, and how to prevent them or reduce them as much as possible.
 
The overall goals of this study are to:
Find out if using chemotherapy with ITT improves survival rates better than using chemotherapy with IT MTX for HR-AL
Compare the effects, good and/or bad, of chemotherapy with ITT to chemotherapy with IT MTX for HR-ALL to find out which is better. In this study, you will get either the ITT or the IT MTX. You will not get both.

Other goals of this study are:
To better understand the effects of cancer treatment in people with HR-ALL.
(Down Syndrome: DS-ALL or DS HR-ALL)

In a recently completed COG study, several patients with DS HR-ALL died from infections during treatment, mainly during Induction and Maintenance. Infections and death are known possible complications of treatment, but more of these complications occurred in patients with Down syndrome. On this study, Induction and Maintenance therapy (described below) have been changed from the usual treatments in an effort to decrease toxicity. We do not know if these changes will decrease toxicity. Therefore, we also will closely monitor patients, with the aim of reducing the number of unintended and unwanted results of treatment (serious side effects) and deaths among children and adolescents with DS HR-ALL.
 
Methotrexate is a cancer-fighting drug that is very important in the treatment of leukemia. During the Interim Maintenance phase of treatment methotrexate is usually given as High dose methotrexate. In “high dose” methotrexate therapy, the same dose of methotrexate is given a total of 4 times (every 2 weeks over a 9-week period). However, because subjects with DS are particularly sensitive to drugs like methotrexate, the High dose methotrexate on this study will be modified to a somewhat lower dose called Intermediate dose methotrexate. We do not know if intermediate dose methotrexate given during Interim Maintenance will be helpful for DS HR-ALL, and it may increase the side effects of treatment.
 
This study also aims to understand the biology of DS HR-ALL better, by testing blood or bone marrow for changes in certain genes. Genes are materials that determine the makeup of the body. We would to learn more about these abnormal changes in genes in patients with DS HR-ALL (called high risk genetic lesions). We would also like to look at levels of white blood cells in the blood (called absolute lymphocyte count) at the end of Induction therapy. This would help us learn more about DS HR-ALL, and may help us to guide therapy for patients in the future.
 
The overall goals of this study are to:
Find out if children with DS HR-ALL will have improved outcomes with a less intense therapy given during the Induction phase of therapy.

Find out if children with DS HR-ALL will have improved outcomes with fewer courses of prednisone and vincristine given during the Maintenance phase of chemotherapy.

Find out if boys with DS HR-ALL will have improved outcomes with approximately 2 years of Maintenance therapy, the same length of treatment given to girls, instead of 3 years of Maintenance therapy, which has been given to boys on some past studies.

Find out if children with DS HR-ALL will have improved outcomes with increased safety and supportive care recommendations.

Find out the effects, good and/or bad, of using intermediate dose methotrexate during Interim Maintenance phase of therapy on children with DS HR-ALL.

Other goals of this study are:
To learn more about the biology of DS HR-ALL through specialized tests.

Who can participate:
Patients must have newly diagnosed B-precursor ALL. Patients with Down syndrome are also eligible.
Patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of ALL or any cancer diagnosed previously, with the exception of steroids and intrathecal cytarabine for the current diagnosis of ALL. Patients cannot have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Patients receiving prior steroid therapy may be eligible for AALL1131.

Additional screening for eligibility will be required.

What will happen during the study:
(Non-Down Syndrome: HR-ALL or VHR-ALL)
 
Random Assignment
People taking part on this study (subjects) will receive 1 of 2 different treatment plans (also called ‘arms’). The treatment plan that you receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. The randomization process will occur after Induction therapy (at the time when your risk status is determined to be HR-ALL) but prior to the start of Consolidation therapy.
 
If you agree to this randomization, you will have an equal chance of being assigned to 1 of the 2 different arms. Some subjects will be randomized to receive treatment on Arm A; others will be randomized to receive treatment on Arm B for all phases of post-Induction therapy. The 2 treatment arms in this study are the same standard or regular therapy for people with HR-ALL except for differences in the type of intrathecal therapy subjects receive.

Arm A: Patients receive therapy that is standard including age adjusted intrathecal methotrexate. This is the standard arm.
Arm B: Patients receive therapy that is standard with triple intrathecal therapy (methotrexate, hydrocortisone and cytosine arabinoside) instead of intrathecal methotrexate. This is the experimental arm.

Induction  
People taking part on this study (subjects) will receive a standard treatment plan during Induction. Induction therapy will be given over 4 weeks.

Post Induction
A number of factors were used to identify you as having HR-ALL. These factors included the results of research tests (FISH, MRD and hypodiploidy) done on leukemia cells before the start of, and during Induction therapy, as well as your age and the presence or absence of leukemia cells in your spinal fluid or brain.
 
The treatment involves cancer fighting medicine called chemotherapy and radiation therapy for patients with testicular disease. Post-Induction treatment on this study is divided into 4 stages: Consolidation, Interim Maintenance, Delayed Intensification and Maintenance.
 
Timing
Female patients are expected to receive treatment on this study for about 2¼ years. Because males receive longer Maintenance therapy, males are expected to receive treatment on this study for about 3¼ years.

(Down Syndrome: DS-ALL or DS HR-ALL)
The treatment plan involves cancer fighting medicine called chemotherapy as well as radiation therapy for people taking part in this study (subjects) with leukemia cells in the testes. Treatment on this study will be given in the following phases: Induction, Consolidation, Interim Maintenance, delayed Intensification and Maintenance. Subjects are people who agree to participate in this study.
 
Studies have shown that subjects who have Down syndrome are more likely to suffer serious side effects from treatment with chemotherapy than subjects without Down syndrome. Subjects with Down syndrome are particularly sensitive to certain chemotherapy medications, such as methotrexate. To help lessen the side effects of methotrexate, you will be given a vitamin called leucovorin, every time you are given methotrexate into your spinal fluid except during Maintenance therapy. You will also be closely monitored throughout your treatment for various side effects. Additionally, you will be receiving treatment during Induction and post-Induction with the following modifications:
 
Induction
During Induction, subjects will receive modified therapy that is less intense than normal. Therapy will be given in such a way that subjects that do not need an additional drug, daunorubicin, will not have to be exposed to the side effects that this drug may have. This will be determined by a bone marrow test that will be done halfway into Induction therapy.
 
All subjects get the same treatment in the first half of Induction, except for the type of steroid used; which will depend on your age. 

If you are less than 10 years old, the steroid dexamethasone will be used

If you are equal to or above 10 years old, prednisone will be used.

After all patients have received Induction treatment for 14 days, a bone marrow test will be done to assess your response to the treatment so far (called early response status). The remaining therapy you get for Induction will depend on your early response status, described below:

• Rapid Early Responders (RER) these subjects respond quickly to treatment. The results of bone marrow tests show signs that the leukemia has been removed and these patients reach remission very soon after the start of treatment. Rapid early responders will therefore continue with Induction therapy as before, for the remainder of Induction therapy.

• Slow Early Responders (SER) these subjects respond to treatment more slowly and take longer to reach remission. Also, once they reach remission, more therapy is needed to maintain that remission. Since SERs are at greater risk of the leukemia coming back, for the remainder of Induction therapy, they will continue with treatment as before, plus they will receive an additional drug called daunorubicin. The dose of daunorubicin that is given on this study is lower than that used on previous studies.

Because chemotherapy can make your blood counts low causing serious side effects like infections and bleeding, you will also get a drug called a myeloid growth factor (example filgrastim) that will help your counts to recover.
 
Post-Induction
During Interim Maintenance, subjects with Down syndrome will be given intermediate dose methotrexate instead of high dose methotrexate because it is known that children with Down syndrome are more sensitive to this drug.

During Maintenance, all subjects will receive the drugs vincristine and prednisone. These drugs are known to have short and long term side effects. Long term side effects are harmful effects seen months or years after you have finished your treatment, and children with Down syndrome have had more serious side effects during Maintenance than other children. Therefore in this study, vincristine and prednisone will be given at regular 12 week intervals (called pulses) for children with Down syndrome, instead of 4 week intervals as will be given to other children on the study, in order to try and reduce these bad effects. In most COG ALL studies, boys are treated for about a year (12 months) longer than girls. In this study, boys will be treated for the same length of time as girls to reduce the risk of serious side effects during Maintenance treatment.
 
Timing
People in this clinical trial are expected to receive treatment on this study for about 2 ½ years. After treatment, you will have follow-up examinations and medical tests.  

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org
 

European Ewing Tumour Working Initiative of National Groups Ewing Tumour Studies 1999 (EURO-E.W.I.N.G.99)  

Purpose of study:
The Children's Oncology Group is joining with several European cooperative groups for this study (Euro E.W.I.N.G –99).

The goals of this study are:
For COG subjects, to compare survival in a randomized study of standard drug therapy and whole lung irradiation versus high dose, intense drug therapy followed by replacement of peripheral blood stem cells (transplant). Some of the subjects in the European Cooperative Groups will also participate in this part of the study.  The overall goal of the study is to improve the outcome of patients with Ewing sarcoma.

Who can participate:
Diagnosis
Patients with isolated pulmonary or pleural metastases at the initial diagnosis of Ewing sarcoma.

Age
Patients must be less than 50 years old at time of study enrollment.  
 
What will happen during the study:
Treatment
The treatment involves cancer fighting medicine called chemotherapy plus radiation therapy. All subjects will receive 6 courses of therapy with vincristine, ifosfamide, doxorubicin and etoposide (VIDE).

Some subjects will need early radiation therapy because of the location of their tumor. Some subjects will receive radiation therapy near the brain or spinal cord. Subjects who receive early radiation therapy or radiation therapy near the brain or spinal cord will be non-randomly assigned to receive standard therapy. Standard therapy consists of an additional 7 courses of therapy with vincristine, actinomycin-D and ifosfamide (VAI) following surgery (if surgery is possible). After completion of therapy with VAI, these subjects will also receive whole lung radiation therapy.
 
Random Assignment
Most subjects will not require early radiation therapy or radiation therapy near the brain or spinal cord. These subjects will be eligible to be randomized to 1 of 2 therapies following surgery (if surgery is possible).The treatment plan that you receive is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. You and your doctor will not pick which treatment you get. The randomization process is described in the COG Family Handbook for Children with Cancer.
 
The treatment plans are:
Standard therapy described above, or Experimental therapy with intensive, high-dose chemotherapy followed by stem cell transplant.

Timing
You will be treated on this study for about 11 months if you receive the standard drug treatment and about 6-8 months if you receive the high-dose transplant treatment. However, subjects will continue to have physical exams and blood tests for a few years after treatment so that researchers can continue to observe any effects of treatment. In addition, we would like to continue to collect some information about how you are doing for as long as you allow us.

Who to contact:
Mark Ranalli, MD, Principal Investigator
(614) 722-3563
Mark.Ranalli@NationwideChildrens.org