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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
JCARH125
JCARH125 + anakinra
Sponsored by
Juno Therapeutics, a Subsidiary of Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring JCARH125, chimeric antigen receptor, multiple myeloma, CAR T cells, B-cell maturation antigen, BCMA, autologous T-cell therapy, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Local Institution - 0006
  • Local Institution - 0007
  • Local Institution - 0059
  • Local Institution - 0010
  • Local Institution - 0060
  • Local Institution - 0042
  • Local Institution - 0016
  • Local Institution - 0061
  • Local Institution - 0053
  • Local Institution - 0009
  • Local Institution - 0005
  • Local Institution - 0062
  • Local Institution - 0054
  • Local Institution - 0038
  • Local Institution - 0013
  • Local Institution - 0001
  • Local Institution - 0058
  • Local Institution - 0023
  • Local Institution - 0018
  • Local Institution - 0055

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

JCARH125

JCARH125 + anakinra

Arm Description

Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125

Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125

Outcomes

Primary Outcome Measures

Phase 1: Incidence of dose-limiting toxicities (DLTs)
Proportion of subjects with adverse events meeting DLT criteria
Phase 1: Incidence and severity of adverse events
Proportion of subjects with adverse events overall and by severity grade
Phase 1: Incidence and severity of clinically significant laboratory abnormalities
Proportion of subjects with clinically significant laboratory abnormalities overall and by severity grade
Phase 1 Anakinra Cohort only: Incidence and severity of Grade 2 or higher cytokine release syndrome (CRS)
Proportion of subjects with Grade 2 or higher CRS
Phase 1 Anakinra Cohort only: Percentage of subjects with no CRS on Days 1, 2, or 3 following JCARH125 infusion
Proportion of subjects with no CRS on Days 1, 2, or 3 following JCARH125 infusion
Phase 1 Anakinra Cohort only: Time to onset of Grade 2 or higher CRS
Median time to onset of Grade 2 or higher CRS
Phase 2: Overall response rate
Proportion of subjects with a partial response or better by International Myeloma Working Group (IMWG) criteria

Secondary Outcome Measures

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

Full Information

First Posted
February 6, 2018
Last Updated
October 19, 2023
Sponsor
Juno Therapeutics, a Subsidiary of Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT03430011
Brief Title
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
Acronym
EVOLVE
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2018 (Actual)
Primary Completion Date
March 30, 2023 (Actual)
Study Completion Date
March 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Juno Therapeutics, a Subsidiary of Celgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
JCARH125, chimeric antigen receptor, multiple myeloma, CAR T cells, B-cell maturation antigen, BCMA, autologous T-cell therapy, immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
169 (Actual)

8. Arms, Groups, and Interventions

Arm Title
JCARH125
Arm Type
Experimental
Arm Description
Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125
Arm Title
JCARH125 + anakinra
Arm Type
Experimental
Arm Description
Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125
Intervention Type
Biological
Intervention Name(s)
JCARH125
Intervention Description
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by one dose of JCARH125 administered intravenously (IV).
Intervention Type
Biological
Intervention Name(s)
JCARH125 + anakinra
Intervention Description
Participants will undergo leukapheresis to isolate PBMCs for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by two doses of anakinra administered subcutaneously and one dose of JCARH125 administered IV. Subjects receive anakinra for 5 consecutive days following JCARH125 infusion.
Primary Outcome Measure Information:
Title
Phase 1: Incidence of dose-limiting toxicities (DLTs)
Description
Proportion of subjects with adverse events meeting DLT criteria
Time Frame
21 days
Title
Phase 1: Incidence and severity of adverse events
Description
Proportion of subjects with adverse events overall and by severity grade
Time Frame
2 years
Title
Phase 1: Incidence and severity of clinically significant laboratory abnormalities
Description
Proportion of subjects with clinically significant laboratory abnormalities overall and by severity grade
Time Frame
2 years
Title
Phase 1 Anakinra Cohort only: Incidence and severity of Grade 2 or higher cytokine release syndrome (CRS)
Description
Proportion of subjects with Grade 2 or higher CRS
Time Frame
2 years
Title
Phase 1 Anakinra Cohort only: Percentage of subjects with no CRS on Days 1, 2, or 3 following JCARH125 infusion
Description
Proportion of subjects with no CRS on Days 1, 2, or 3 following JCARH125 infusion
Time Frame
2 years
Title
Phase 1 Anakinra Cohort only: Time to onset of Grade 2 or higher CRS
Description
Median time to onset of Grade 2 or higher CRS
Time Frame
2 years
Title
Phase 2: Overall response rate
Description
Proportion of subjects with a partial response or better by International Myeloma Working Group (IMWG) criteria
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Phase 1 and Phase 2: Maximum concentration (Cmax) of JCARH125 in the blood
Time Frame
2 years
Title
Phase 1 and Phase 2: Time to maximum concentration (Tmax) of JCARH125 in the blood
Time Frame
2 years
Title
Phase 1 and Phase 2: Area under the concentration vs time curve (AUC) of JCARH125 in the blood
Time Frame
2 years
Title
Phase 1 and Phase 2: Duration of persistence of JCARH125 CAR T cells in the blood
Time Frame
2 years
Title
Phase 1: Overall response rate
Description
Proportion of subjects with a partial response (PR) or better by IMWG criteria
Time Frame
2 years
Title
Phase 1 and Phase 2: Complete response (CR) rate
Description
Proportion of subjects with a CR by IMWG criteria
Time Frame
2 years
Title
Phase 2: Duration of response
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
Time Frame
2 years
Title
Phase 2: Duration of CR
Description
Time from first sCR or CR to the earlier date of PD or death due to any cause
Time Frame
2 years
Title
Phase 2: incidence and severity of adverse events
Description
Proportion of subjects with adverse events overall and by severity grade
Time Frame
2 years
Title
Phase 2: Incidence and severity of clinically significant laboratory abnormalities
Description
Proportion of subjects with clinically significant laboratory abnormalities overall and by severity grade
Time Frame
2 years
Title
Phase 2: Overall survival
Description
Time from JCARH125 infusion until death
Time Frame
2 years
Title
Phase 2: Progression-free survival
Description
Time from JCARH125 infusion until the earliest of date of death or disease progression as assessed by IMWG criteria
Time Frame
2 years
Title
Phase 2: Time to response
Description
Time from JCARH125 infusion to first documentation of PR or better
Time Frame
2 years
Title
Phase 2: Time to CR
Description
Time from JCARH125 infusion to first documentation of CR or better
Time Frame
2 years
Title
Phase 2 (excluding Phase 2a): Changes in measures of health-related quality of life (HRQoL)
Description
Change from baseline in HRQoL
Time Frame
2 years
Title
Phase 2 (excluding Phase 2a): Numbers of days in the intensive care unit (ICU)
Time Frame
2 years
Title
Phase 2 (excluding Phase 2a): Number of non-ICU inpatient days
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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): Autologous stem cell transplant A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination 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. Subjects must have measurable disease. Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required). Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function 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: 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. Subjects who have received prior BCMA-directed T-cell engager therapy. Subjects who have received prior BCMA-directed antibody-drug conjugate therapy. Exclusion Criteria: Subjects with known active or history of CNS involvement by malignancy 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 Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant 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. 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]) Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for subjects enrolled in Phase 2a cohorts) Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in Phase 2a cohorts) 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 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. 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 Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to subjects in Phase 1 Anakinra Cohort) History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald Dubowy, MD
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 0006
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
10016
Country
United States
Facility Name
Local Institution - 0007
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Local Institution - 0059
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1678
Country
United States
Facility Name
Local Institution - 0010
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Local Institution - 0060
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Local Institution - 0042
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Local Institution - 0016
City
New Lenox
State/Province
Illinois
ZIP/Postal Code
60451
Country
United States
Facility Name
Local Institution - 0061
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Local Institution - 0053
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Local Institution - 0009
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Local Institution - 0005
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Local Institution - 0062
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Local Institution - 0054
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Local Institution - 0038
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Local Institution - 0013
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Local Institution - 0001
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Local Institution - 0058
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201-3098
Country
United States
Facility Name
Local Institution - 0023
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Local Institution - 0018
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Local Institution - 0055
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

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

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