Acute myeloid leukemia (AML) accounts for approximately 20 percent of leukemias occurring in children and adolescents, and only 60-65% of these patients are cured with frontline therapies. Clinical outcomes for children with AML have improved minimally during the past four decades despite maximally intensive chemotherapy, hematopoietic stem cell transplantation, and optimized supportive care.

Chemotherapy resistance and AML relapse remain major sources of childhood cancer-associated mortality, which highlights a continued need for alternative treatment approaches. The remarkable recent success of antibody-based and cellular immunotherapies in children and adults with relapsed/refractory B-acute lymphoblastic leukemia has inspired hope for similar accomplishments in pediatric patients with AML, and major bench-to-bedside research efforts specifically in AML immunotherapy are ongoing at CHOP.

A first-in-child/first-in-human CD33 CAR T cell phase 1 trial (NCT03971799) for children and adolescents/young adults (AYAs) with relapsed or chemotherapy-refractory acute myeloid leukemia (AML) opened in January 2020 at Children’s Hospital of Philadelphia (CHOP) and the National Cancer Institute (NCI) with subsequent planned expansion to Children’s Hospital Colorado (CHCO), Seattle Children’s Hospital, Boston Children’s Hospital, and Children’s Hospital of Los Angeles. This “team science” trial is sponsored by the Pediatric Bone Marrow Transplant Consortium and is led by Drs. Nirali Shah (NCI), Richard Aplenc (CHOP), Terry Fry (CHCO), and Sarah Tasian (CHOP). Importantly, this trial is a direct bench-to-bedside translation of collaborative preclinical studies conducted in the Fry and Tasian laboratories as part of the multi-institutional St. Baldrick’s Foundation/American Association for Cancer Research (AACR)/Stand Up to Cancer (SU2C) Pediatric Dream Team research program led by Drs. John Maris (CHOP) and Crystal Mackall (Stanford). The remarkable preclinical activity of CD33 CAR T cells against AML cell lines and in childhood AML patient-derived xenograft mouse models was reported by Dr. Tasian at the 50th annual Congress of the International Society of Paediatric Oncology in November 2018 in Kyoto, Japan.

Additional preclinical studies of CAR T cells targeting other high-risk childhood AML and ALL antigens are ongoing in the Tasian and Fry laboratories via research grants from the National Cancer Institute, the Department of Defense, AACR/SU2C, and biotechnology partners. The Aplenc research group is also conducting proteomic studies of childhood AML with a goal of new immunotherapeutic target identification. These robust laboratory research programs have provided critical preclinical data that have informed development of additional phase 1 CAR T cell immunotherapy trials for children and AYAs with high-risk subtypes of ALL and AML that are planned to open in 2020 and 2021.

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Cancer Immunotherapy Studies

The Cancer Immunotherapy Program has several clinical trials available to qualified patients.