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FDA Grants ‘Breakthrough Therapy’ Designation to T-Cell Treatment for Leukemia
The FDA has granted “breakthrough therapy” status to JCAR015 (Juno Therapeutics), a chimeric antigen receptor (CAR) product candidate. The designation applies to the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
The FDA’s “breakthrough therapy” designation was created to help accelerate the development and review of new drugs for serious or life-threatening conditions. The designation comes with potential benefits, including eligibility for priority review. It is granted to applicants when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinical endpoints.
JCAR015 is based on CAR technology, which employs the body’s immune system to attack cancer cells. In the treatment, T cells are removed from the patient’s blood; a gene is inserted into the cells via a weakened virus, which targets the cells to the B-cell–specific antigen CD19; and the genetically modified T cells are returned to the body. These cells are now able to recognize and kill cancer cells.
A phase I, open-label trial is currently under way at the Memorial Sloan Kettering Cancer Center in New York City. In this study, an estimated 40 adults (18 years of age or older) with B-ALL will be treated with different doses of modified T cells depending on the amount of disease at the time of T-cell infusion.
Initially, the patients will undergo leukapheresis. CD3+ T cells will be isolated from the leukapheresis product, and transduced with the 19–28z chimeric receptor and expanded. All relapsed and refractory patients will receive re-induction chemotherapy whenever feasible to reduce the tumor burden before the T-cell infusion.
Once the patients recover from the toxicities of the re-induction chemotherapy, their disease status will be re-evaluated by repeating bone marrow aspirate or biopsy. The patients will then receive conditioning chemotherapy (a minimum of 2 weeks from the end of re-induction chemotherapy), followed 2 to 7 days later by the 19–28z+ T cells.
The patients will be treated in two cohorts with different doses of T cells, according to the amount of disease immediately prior to the T-cell infusion. Patients in cohort 1 (< 5% blasts in the bone marrow) will continue to receive 10^6 19–28z+ T cells/kg, as previously. Patients in cohort 2 (≥ 5% blasts in the bone marrow) will receive the reduced dose of 1 x 106 19–28z+ T cells/kg.
Data from this study will be presented at the 54th Annual Meeting of the American Society of Hematology, to be held next week in San Francisco.
Sources: Juno Therapeutics; November 24, 2014; and ClinicalTrials.gov; June 2014.