Columbus, OH — March 2018
Children with relapsed or refractory leukemia enrolled in early phase clinical trials are at high risk for life-threatening treatment-related toxicity, especially infections. In addition to causing serious health problems for patients, such treatment-related toxicity can also result in the removal of patients from trials, preventing them from receiving the full clinical benefit of the therapy.
To address this challenge, the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium recently created a Supportive Care Committee (SCC). The goals of the SCC, outlined in a recent article in the journal Pediatric Hematology and Oncology, are to provide evidence-based supportive care guidelines to support the testing of promising new therapeutic agents for relapsed or refractory leukemia.
Jeffery Auletta, MD, director of the Blood and Marrow Transplant Program at Nationwide Children's Hospital, wrote the statement of the SCC’s mission with Etan Orgel, MD, director of the Medical Supportive Care Service at Children’s Hospital of Los Angeles. The two doctors are the committee’s co-chairs.
Drs. Auletta and Orgel reviewed the outcomes of 12 TACL phase I trials. They found a high rate of serious adverse events experienced by patients with relapsed/refractory leukemia enrolled in these trials. Infections were an especially common complication.
“Some kids may not actually benefit from any anti-leukemia effect due to significant toxicities associated with the therapeutic intervention itself,” says Dr. Auletta, also an associate professor of Pediatrics at The Ohio State University College of Medicine. “These complications limit the ability to complete early phase clinical trials due to the patient’s inherent susceptibility to infection or other complications.”
As a result, the premature exit of these patients from trials makes it difficult to fully judge the efficacy of the therapeutic intervention. Such occurrence of treatment-related toxicity might compromise new therapeutic agents from moving forward into clinical development despite their potential anti-leukemic effect.
TACL initiated the SCC to address some of these issues and to develop strategies to mitigate toxicity on early phase clinical trials. Initial efforts have focused on identifying children at high risk for infection before they begin a clinical trial.
To better support this goal in the future, the SCC has proposed the development of a Pediatric Early Phase Co-Morbidity Index, which would measure risk for treatment-related toxicity prior to the start of a clinical trial.
“It would be similar to something we have right now in the transplant world called the Transplant Co-Morbidity Index,” says Dr. Auletta. “There are probably certain kids that are at higher risk for contracting infections; and we might suggest either not enrolling them onto an early phase clinical trial or supporting them with certain prophylaxis or other supportive care to avoid life-threatening complications.”
Dr. Auletta says Nationwide Children’s is already taking steps to mitigate the potential for treatment-related toxicity. Dr. Auletta also leads the Host Defense Program, the mission of which is to reduce infection-related complications and mortality in immunocompromised children.
“That’s a concrete example of something here at Nationwide Children’s that is making a difference,” says Dr. Auletta. “This program has been instrumental in improving outcomes in immunocompromised patients like cancer and stem cell transplant patients.”
In addition, Nationwide Children’s and The Ohio State University Comprehensive Cancer Center are home to the Cellular Therapy and Cancer Immunotherapy Program led by Dean Lee, MD, PhD, which has the goal of using novel cell therapies as alternatives to conventional chemotherapies, particularly for relapsed or refractory leukemia. These cell therapies often target the cancer and potentially cause fewer toxicity-related complications.
“With the Cell Therapy Program, we now have the capability to provide relapsed or refractory leukemia patients with cell therapies that target their leukemia as an alternative to chemotherapy,” says Dr. Auletta. “Such transformational clinical care and technology as well as holistic, compassionate care is what makes Nationwide Children's Hospital so uniquely special.”
Orgel, E and Auletta, J J (2017). TACL’ing supportive care needs in pediatric early phase clinical trials for acute leukemia: A report from the therapeutic advances in childhood leukemia & lymphoma (TACL) consortium supportive care committee.Pediatric Hematology and Oncology.2017 Sep - Oct; 34 (6-7): 409-417.