Dana-Farber/Boston Children's joins immunotherapy clinical trial for children with ALL

Dana-Farber/Boston Children's Cancer and Blood Disorders Center has joined a clinical trial of immunotherapy for children with relapsed or treatment-resistant acute lymphoblastic leukemia (ALL). Led by Memorial Sloan Kettering Cancer Center (MSKCC), the trial is one of several nationally that are evaluating cancer immunotherapy, a treatment approach -- hailed by Science magazine as their Breakthrough of the Year in 2013 -- that triggers a patient's immune system to attack his or her cancer cells. Dana-Farber/Boston Children's is the only site in New England to offer this experimental approach for children and adolescents whose ALL has relapsed multiple times or never gone into remission.

The innovative trial starts with a patient's own infection-fighting T-cells. These cells are collected and modified using gene therapy techniques to produce a cancer-hunting protein called a chimeric antigen receptor (CAR). Once infused back into the patient, the CAR then prompts the modified T-cells to attack leukemia cells by seeking out and recognizing a protein they carry on their surface. The CAR also spurs the modified T-cells to divide and grow once they come in contact with ALL cells, fueling a more robust immune response.

"There has been evidence for many years that the immune system can be used to help control leukemia, but we have yet to find the best way to harness it to treat disease," said Lewis Silverman, MD, clinical director of the Hematologic Malignancies Center at Dana-Farber/Boston Children's and the local lead investigator on the trial. "CAR-modified T-cell clinical trials have shown promising results in adults and children with leukemias, and we are very excited to test this treatment in children and adolescents with ALL."

This pediatric CAR T-cell trial is available only at Dana-Farber/Boston Children's and MSKCC. The trial is open to patients up to age 26 with relapsed B-cell ALL who have not yet undergone a hematopoietic stem cell transplant. The trial joins Dana-Farber/Boston Children's already robust portfolio of clinical trials for both leukemia and gene therapy.

Approximately 2,900 children in the United States are diagnosed each year with ALL, the most common cancer of childhood. Although 80-90 percent of patients go on to become long-term survivors, 15-20 percent of children who achieve an initial complete remission later experience a relapse. The prognosis for these patients depends on a number of factors, including the site of relapse, length of time between initial diagnosis and relapse, and biological features of the relapsed cells.

The Phase I trial is the first clinical step in the Food and Drug Administration's process for approving a new drug or treatment. The goal is to establish the treatment's safety in a small group of patients, with an eye toward larger studies of safety and efficacy should the Phase I trial succeed. Each trial participant will be followed very closely for side effects as well as treatment response. Because the trial involves gene therapy, participants will be followed for 15 years following treatment.