The chimeric antigen receptor (CAR) T-cell therapy JCAR015 has received a breakthrough therapy designation from the Food and Drug Administration as a treatment for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to a statement released by Juno Therapeutics, the company developing the adoptive T-cell therapy.
In data from a clinical trial that examined the therapy in 16 patients with ALL, the complete response rate was 88 percent, according to findings presented at the 2014 annual meeting of the American Association for Cancer Research (AACR). Patients who responded to the therapy became eligible for a potentially curative allogeneic hematopoietic stem cell transplant.
In early April 2014, five early-phase clinical trials exploring CAR T-cell therapies manufactured by Juno Therapeutics were suspended temporarily in response to the deaths of two patients with adult B-cell acute ALL. However, on April 19 the studies resumed following adjustments to the safety protocols to address the occurrence of severe cytokine release syndrome.
In general, cytokine release syndrome is a common phenomenon observed with T-cell therapies, which is thought to indicate that the treatment is working. The rare side effect is caused following infusion of the therapy into the patient. At this point, the T cells expand and cytokines are released, causing systemic symptoms such as fever, nausea, chills, hypotension, headache and rash, among others.
In a report on the drug at the 2014 AACR meeting, researchers noted that severe cytokine release syndrome could be detected using a readily available laboratory test. Moreover, once detected, cytokine release syndrome could be treated using corticosteroids or interleukin-6 receptor blockade.
Upon addressing early safety concerns, the clinical trial program resumed with several phase 1/2 studies currently enrolling participants. A study exploring JCAR015 is currently enrolling at the Memorial Sloan Kettering Cancer Center to assess the T-cell therapy in patients with B cell ALL (NCT01044069). Additionally, another trial at the same center is assessing JCAR015 in patients with aggressive B cell non-Hodgkin lymphoma (NCT01840566).
Other CAR T-cell therapies developed by Juno Therapeutics are being looked at in clinical trials. JCAR017 will be examined in a phase 1/2 trial of pediatric and young adult patients with relapsed/refractory CD19-positive leukemia (NCT02028455), whereas JCAR014 will be looked at in a phase 1/2 trial of patients with CD19-positive chronic lymphocytic leukemia, ALL and non-Hodgkin lymphoma (NCT01865617).
[Breakthrough status explained: FDA’s Breakthrough Therapy Designation Aims to Speed Drug Approvals]