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A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma

NCT04133636

Description:

The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma
  • Official Title: A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CR108581
  • SECONDARY ID: 2018-004124-10
  • SECONDARY ID: 68284528MMY2003
  • NCT ID: NCT04133636

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
JNJ-68284528JNJ-68284528
LenalidomideJNJ-68284528
DaratumumabJNJ-68284528
BortezomibJNJ-68284528
DexamethasoneJNJ-68284528

Purpose

The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.

Detailed Description

      Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig)
      proteins or protein fragments (M proteins) that have lost their function. The main aim of the
      study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings.
      JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets
      B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or
      equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment);
      a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and
      post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of
      JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101
      and up to the end of each study cohort). Safety evaluations will include a review of adverse
      events, laboratory test results, vital sign measurements, physical examination findings
      (including neurologic examination), assessment of cardiac function, immune effector
      cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern
      Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include
      measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations,
      skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. For
      certain participants (those without measurable disease in serum or urine) efficacy will be
      assessed via imaging: positron emission tomography/ computed tomography (PET/CT) or whole
      body magnetic resonance imaging (MRI). The overall duration of the study is up to 2.5 years.
    

Trial Arms

NameTypeDescriptionInterventions
JNJ-68284528ExperimentalSingle group assignment- After lymphodepletion, JNJ-68284528 will be administered as a single infusion to participants in cohort A (Progressive disease after 1-3 prior lines of therapy), cohort B (Early relapse after front-line), cohort C (Relapsed/refractory multiple myeloma after proteasome inhibitor [PI], immunomodulatory [IMiD], anti-CD38, and anti-B-cell maturation antigen [BCMA] therapy) and cohort D (Less than CR after autologous stem cell transplantation [ASCT] front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide). Participants in cohort E (Newly diagnosed multiple myeloma, transplant not planned, high risk disease) will first be administered with quadruplet induction regimen of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd), followed by lymphodepletion and JNJ-68284528, followed by a consolidation regimen of daratumumab and lenalidomide (D+R).
  • JNJ-68284528
  • Lenalidomide
  • Daratumumab
  • Bortezomib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a
             proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide
             refractory per International Myeloma Working Group (IMWG) guidelines

          -  Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease
             progression per IMWG criteria less than or equal to (<=) 12 months after treatment
             with autologous stem cell transplantation (ASCT) or <=12 months from the start of
             anti-myeloma therapy for participants who have not had an ASCT

          -  Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and
             B-cell maturation antigen (BCMA)-directed therapy

          -  Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total
             cycles of initial therapy, including induction, high-dose therapy, and ASCT with or
             without consolidation

          -  Cohort E: Have newly diagnosed multiple myeloma without prior therapy and classified
             as high risk per International Staging System (ISS) stage III criteria, defined as:
             beta 2 microglobulin greater than (>) 5.5 milligram per litre (mg/L)

        Cohort A, B, C, E:

          -  Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram
             per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours

          -  Light chain multiple myeloma in whom only measurable disease is by serum free light
             chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal
             serum immunoglobulin kappa lambda FLC ratio

          -  Cohort A, B, C: For participants with neither serum nor urine measurable disease,
             baseline positron emission tomography/ computed tomography (PET/CT) or whole body
             magnetic resonance imaging (MRI) may be used to satisfy the measurable disease
             criteria

          -  Cohort A, B, C, D, E: Eastern Cooperative Oncology Group (ECOG) performance status
             grade of 0 or 1

        Exclusion Criteria:

        - Cohort A, B, D: Any therapy that is targeted to BCMA

        Cohort A, B, C, D:

          -  Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any
             target

          -  Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or
             to Grade 1 or less except for alopecia or peripheral neuropathy

          -  Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone
             within the 7 days (Cohort A, B, C) or 14 days (Cohort D) prior to apheresis

          -  Serious underlying medical condition, such as (a) evidence of active viral or
             bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic
             fungal infection; (b) active autoimmune disease or a history of autoimmune disease
             within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d)
             any history of Parkinson's disease or other neurodegenerative disorder

          -  Cohort A, B, C, D, E: Known active, or prior history of central nervous system (CNS)
             involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Negative Minimal Residual Disease (MRD)
Time Frame:At least 1 year after JNJ-68284528 infusion on Day 1
Safety Issue:
Description:MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate as defined by the International Myeloma Working Group (IMWG) criteria.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
Measure:VGPR or Better Rate
Time Frame:Up to 2 years
Safety Issue:
Description:The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 2 years
Safety Issue:
Description:CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
Measure:Duration of Response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.
Measure:Time to Response (TTR)
Time Frame:Up to 2 years
Safety Issue:
Description:TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
Measure:MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR)
Time Frame:12 months
Safety Issue:
Description:MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.
Measure:Time to MRD Negativity
Time Frame:Up to 2 years
Safety Issue:
Description:Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.
Measure:Duration of MRD Negativity
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).
Measure:MRD Negative Rate Across Clinical Response
Time Frame:Up to 2 years
Safety Issue:
Description:MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.
Measure:Number of Participants with Adverse Events by Severity
Time Frame:Up to 2 years
Safety Issue:
Description:An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
Measure:Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
Time Frame:Up to 2 years
Safety Issue:
Description:An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measure:Number of Participants with Laboratory Abnormalities
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with laboratory abnormalities will be reported.
Measure:Number of Participants with Vital Sign Abnormalities
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with vital sign abnormalities will be reported.
Measure:Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA
Time Frame:Up to 1 year
Safety Issue:
Description:Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.
Measure:Systemic Inflammatory Cytokine Concentrations
Time Frame:Up to 1 year
Safety Issue:
Description:Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.
Measure:Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
Time Frame:Up to 1 year
Safety Issue:
Description:Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Measure:Number of Participants with Anti-JNJ-68284528 Antibodies
Time Frame:Up to 1 year
Safety Issue:
Description:Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

August 12, 2020