Date: 2016-11-23
Type of information: Halting of the trial
phase: 2
Announcement: halting of the trial - clinical hold
Company: Juno Therapeutics (USA - WA)
Product: JCAR015 - autologous CD3+ T cells transduced with retroviral vector containing a chimeric antigen receptor directed against CD19 (Autologous CD3+ T cells containing CD19 chimeric antigen receptor)
Action
mechanism: cell therapy/immunotherapy product/gene therapy/CAR-T cell therapy. JCAR015, Juno's most advanced product candidate, is an autologous chimeric antigen receptor (CAR) T cell immunotherapy targeting CD19, a protein expressed on the surface of most B cell leukemias and lymphomas. JCAR015 is based on chimeric antigen receptor (CAR) technology. T cells are removed from blood, transduced with retroviral vector containing a chimeric antigen receptor directed against CD19, and then put back in the body. This gene will produce proteins in the T cells that help the T cells recognize the leukemia cells and possibly kill them.
Disease: acute lymphoblastic leukemia (ALL)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This single-arm, multicenter Phase 2 trial will treat adult patients who have relapsed or refractory B-ALL with an infusion of the patient's own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to leukemia cells that express the CD19 protein on the cell surface. The study will determine if these modified T cells (called JCAR015) help the body's immune system eliminate leukemia cells. The trial will also study the safety of treatment with JCAR015, how long JCAR015 cells stay in the patient's body, the extent to which JCAR015 eliminates minimal residual disease, and the impact of this treatment on survival. (NCT02535364)
Latest
news: * On November 23, 2016, Juno Therapeutics announced that it has voluntarily placed on hold the Phase II clinical trial (ROCKET trial) of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia. The clinical hold was initiated after two patients suffered cerebral edema earlier this week. One patient died and as of last night the other is not expected to recover. Juno has notified the FDA of the voluntary hold and is working with the agency and the Data and Safety Monitoring Board to determine next steps. The company is assessing data from the cases and the trial and is evaluating its options regarding the JCAR015 program. * On July 12, 2016, Juno Therapeutics announced that the FDA has removed the clinical hold on the Phase II clinical trial of JCAR015 ( ROCKET trial) in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia. Under the revised protocol, the ROCKET trial will continue enrollment using JCAR015 with cyclophosphamide pre-conditioning only. * On July 7, 2016, Juno Therapeutics announced that it has received notice from the FDA that a clinical hold has been placed on the Phase II clinical trial of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r ALL), known as the “ROCKET” trial. The clinical hold was initiated after two patient deaths last week, which followed the recent addition of fludarabine to the pre-conditioning regimen. * On July 30, 2015, Juno Therapeutics announced the FDA cleared its investigational new drug (IND) application for JCAR015 for treatment of adult patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). The IND enables Juno to initiate a multi-center, pivotal Phase 2 trial evaluating JCAR015 in patients with r/r ALL. The trial is scheduled to begin in the near term, with the potential to file for registration by late 2016 or early 2017.
Juno’s trials and plans for its other CD19-directed CAR T cell product candidates, including JCAR017, are not affected.
Juno has proposed to the FDA to continue the ROCKET trial using JCAR015 with cyclophosphamide pre-conditioning alone. In response, the FDA has requested that Juno submit, as a Complete Response to the Clinical Hold: a revised patient informed consent form, a revised investigator brochure, a revised trial protocol, and a copy of the presentation made to the agency yesterday. Juno will submit the requested information to the FDA this week. Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates, including JCAR017, are not affected.
The initial trial to be conducted under this IND is titled "Protocol 015001: A Phase 2, single-arm, Multicenter Trial to Determine the Efficacy and Safety of JCAR015 in Adult Subjects with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (The ROCKET Study)." The primary objective of this trial is to evaluate the efficacy of JCAR015 as measured by overall remission rate in subjects with morphologic evidence of disease (5% or more leukemic blasts in the bone marrow). The trial will also evaluate the safety and tolerability of the therapy. The study will open at 14 clinical sites in the U.S. and enroll approximately 90 subjects in order to achieve 50 subjects with morphologic disease following salvage chemotherapy.
