Clinical Trials /

Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma

NCT03430011

Description:

This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in subjects who receive prophylactic treatment with anakinra will be evaluated in a separate Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
  • Official Title: Protocol H125001: An Open-Label Phase 1/2 Study of JCARH125, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: H125001
  • NCT ID: NCT03430011

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
JCARH125JCARH125
JCARH125 + anakinraJCARH125 + anakinra

Purpose

This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in subjects who receive prophylactic treatment with anakinra will be evaluated in a separate Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.

Trial Arms

NameTypeDescriptionInterventions
JCARH125ExperimentalSubjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125
  • JCARH125
JCARH125 + anakinraExperimentalSubjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125
  • JCARH125 + anakinra

Eligibility Criteria

        Key Inclusion Criteria:

          1. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory (R/R) disease.
             Participants must have received at least 3 prior anti-myeloma treatment regimens.
             Participants must have previously received all of the following therapies and must be
             refractory to the last line of therapy prior to entering the study (not applicable to
             Phase 2a):

               1. Autologous stem cell transplant

               2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide,
                  pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib),
                  either alone or in combination

               3. Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy

             Subjects who have received prior allogeneic stem cell transplant or donor lymphocyte
             infusion at least 100 days before enrollment with no signs of acute or chronic
             graft-versus-host disease (GVHD) will be considered eligible. Subjects who were not
             candidates to receive one or more of the above treatments (ie, contraindicated) are
             eligible.

          2. Subjects must have measurable disease.

          3. Subject must be willing to provide fresh bone marrow biopsy samples during Screening
             (and prior to study treatment, if required).

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          5. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function

          6. Phase 2a cohorts only - Subjects with R/R MM who have been previously treated with
             prior BCMA-directed anti-myeloma therapy, achieved at least a partial response (PR)
             and progressed on the following treatment:

               1. Subjects who have received prior BCMA-directed CAR T-cell therapy. The last CAR
                  T-cell therapy must have been received at least 6 months prior to JCARH125
                  screening.

               2. Subjects who have received prior BCMA-directed T-cell engager therapy.

               3. Subjects who have received prior BCMA-directed antibody-drug conjugate therapy.

        Exclusion Criteria:

          1. Subjects with known active or history of CNS involvement by malignancy

          2. Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL);
             Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy,
             Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic
             amyloidosis

          3. Subjects who are considered eligible to receive and have not refused an autologous
             stem cell transplant

          4. History of another primary malignancy that has not been in remission for at least 3
             years. The following are exempt from the 3-year limit: non-melanoma skin cancer,
             curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or
             a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has
             been completely resected.

          5. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors,
             methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such
             as anti-IL-6 or anti-IL-6 receptor [IL-6R])

          6. Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for
             subjects enrolled in Phase 2a cohorts)

          7. Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in
             Phase 2a cohorts)

          8. History or presence of clinically relevant CNS pathology such as epilepsy, seizure,
             paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease,
             cerebellar disease, organic brain syndrome, or psychosis

          9. Untreated or active infection at time of initial screening, at the time of
             leukapheresis, within 72 hrs before lymphodepletion, or 5 days before JCARH125
             infusion.

         10. History of any of the following cardiovascular conditions within 6 months of
             screening: Class III or IV heart failure as defined by the New York Heart Association
             (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial
             arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac
             disease

         11. Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to
             subjects in Phase 1 Anakinra Cohort)

         12. History of severe immediate hypersensitivity reaction to any of the protocol-mandated
             or recommended agents used in this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Incidence of dose-limiting toxicities (DLTs)
Time Frame:21 days
Safety Issue:
Description:Proportion of subjects with adverse events meeting DLT criteria

Secondary Outcome Measures

Measure:Phase 1 and Phase 2: Maximum concentration (Cmax) of JCARH125 in the blood
Time Frame:2 years
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Time to maximum concentration (Tmax) of JCARH125 in the blood
Time Frame:2 years
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Area under the concentration vs time curve (AUC) of JCARH125 in the blood
Time Frame:2 years
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Duration of persistence of JCARH125 CAR T cells in the blood
Time Frame:2 years
Safety Issue:
Description:
Measure:Phase 1: Overall response rate
Time Frame:2 years
Safety Issue:
Description:Proportion of subjects with a partial response (PR) or better by IMWG criteria
Measure:Phase 1 and Phase 2: Complete response (CR) rate
Time Frame:2 years
Safety Issue:
Description:Proportion of subjects with a CR by IMWG criteria
Measure:Phase 2: Duration of response
Time Frame:2 years
Safety Issue:
Description:Time from first response (stringent complete response [sCR], CR, very good partial response [VGPR], or PR) to the earlier date of progressive disease (PD) or death due to any cause
Measure:Phase 2: Duration of CR
Time Frame:2 years
Safety Issue:
Description:Time from first sCR or CR to the earlier date of PD or death due to any cause
Measure:Phase 2: incidence and severity of adverse events
Time Frame:2 years
Safety Issue:
Description:Proportion of subjects with adverse events overall and by severity grade
Measure:Phase 2: Incidence and severity of clinically significant laboratory abnormalities
Time Frame:2 years
Safety Issue:
Description:Proportion of subjects with clinically significant laboratory abnormalities overall and by severity grade
Measure:Phase 2: Overall survival
Time Frame:2 years
Safety Issue:
Description:Time from JCARH125 infusion until death
Measure:Phase 2: Progression-free survival
Time Frame:2 years
Safety Issue:
Description:Time from JCARH125 infusion until the earliest of date of death or disease progression as assessed by IMWG criteria
Measure:Phase 2: Time to response
Time Frame:2 years
Safety Issue:
Description:Time from JCARH125 infusion to first documentation of PR or better
Measure:Phase 2: Time to CR
Time Frame:2 years
Safety Issue:
Description:Time from JCARH125 infusion to first documentation of CR or better
Measure:Phase 2 (excluding Phase 2a): Changes in measures of health-related quality of life (HRQoL)
Time Frame:2 years
Safety Issue:
Description:Change from baseline in HRQoL
Measure:Phase 2 (excluding Phase 2a): Numbers of days in the intensive care unit (ICU)
Time Frame:2 years
Safety Issue:
Description:
Measure:Phase 2 (excluding Phase 2a): Number of non-ICU inpatient days
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Juno Therapeutics, a Subsidiary of Celgene

Trial Keywords

  • JCARH125
  • chimeric antigen receptor
  • multiple myeloma
  • CAR T cells
  • B-cell maturation antigen
  • BCMA
  • autologous T-cell therapy
  • immunotherapy

Last Updated

April 30, 2020