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A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma

NCT04181827

Description:

The purpose of this study is to compare the efficacy of JNJ-68284528 with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma
  • Official Title: A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CR108695
  • SECONDARY ID: 2019-001413-16
  • SECONDARY ID: 68284528MMY3002
  • NCT ID: NCT04181827

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
JNJ-68284528Arm B: JNJ-68284528
PomalidomideArm A: PVd or DPd (Standard Therapy)
BortezomibArm A: PVd or DPd (Standard Therapy)
DexamethasoneArm A: PVd or DPd (Standard Therapy)
DaratumumabArm A: PVd or DPd (Standard Therapy)

Purpose

The purpose of this study is to compare the efficacy of JNJ-68284528 with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).

Detailed Description

      Multiple myeloma is a malignant plasma cell disorder diagnosed annually in approximately
      86,000 participants worldwide. JNJ-68284528 is an autologous chimeric antigen receptor T-cell
      (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the
      surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis for this
      study is that JNJ-68284528 will significantly improve progression free survival (PFS)
      compared with standard therapy (PVd or DPd), in participants who have previously received 1
      to 3 prior line(s) of therapy, that included a proteasome inhibitor (PI) and an
      immunomodulatory drug (IMiD) and who are refractory to lenalidomide. This study will be
      conducted in 3 phases: Screening (up to 28 days before randomization), Treatment, and
      Follow-Up. Assessment like patient-reported outcome(s) (PROs) assessments, electrocardiogram
      (ECG), vital signs, pharmacokinetic will be performed during the study. Safety evaluations
      will include review of adverse events, laboratory test results, vital sign measurements,
      physical examination findings, and assessments of cardiac function, Immune Effector
      Cell-associated Encephalopathy (only for Arm B), and Eastern Cooperative Oncology Group
      performance status. Safety and efficacy data will be periodically reviewed by an Independent
      Data Monitoring Committee. The duration of the study is approximately 6 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: PVd or DPd (Standard Therapy)ExperimentalParticipants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier.
  • Pomalidomide
  • Bortezomib
  • Dexamethasone
  • Daratumumab
Arm B: JNJ-68284528ExperimentalParticipants will receive one cycle of bridging therapy (PVd or DPd) and a second cycle of PVd or DPd may be administered per communication between the investigator and sponsor along with conditioning regimen (cyclophosphamide 300 milligram [mg]/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily, for 3 days), and JNJ-68284528 infusion 0.75 * 10^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg).
  • JNJ-68284528

Eligibility Criteria

        Inclusion Criteria:

          -  Measurable disease at screening as defined by any of the following: (a) 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; or (b) Light
             chain multiple myeloma without measurable M-protein in the serum or the urine: Serum
             free light chain >=10 mg/dL and abnormal serum free light chain ratio

          -  Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and
             an immunomodulatory drug (IMiD)

          -  Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria
             based on investigator's determination on or within 6 months of their last regimen

          -  Be refractory to lenalidomide per IMWG consensus guidelines (progression on or within
             60 days of completing lenalidomide therapy). Progression on or within 60 days of the
             last dose of lenalidomide given as maintenance will meet this criterion. For
             participants with more than 1 prior line of therapy, there is no requirement to be
             lenalidomide refractory to the most recent line of prior therapy

          -  Have clinical laboratory values meeting the following criteria during the Screening
             Phase (re testing is allowed but the below criteria must be met in the latest test
             prior to randomization):

               1. Hemoglobin >=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7
                  days before the laboratory test; recombinant human erythropoietin use is
                  permitted);

               2. Absolute neutrophil count (ANC) >=1 * 10^9 per liter (L) (without recombinant
                  human granulocyte colony-stimulating factor [G-CSF] within 7 days and without
                  pegylated G-CSF within 14 days of the laboratory test);

               3. Platelet count >=75 * 10^9/L (without prior platelet transfusion within 7 days
                  before the laboratory test) in subjects in whom less than (<) 50 percent (%) of
                  bone marrow nucleated cells are plasma cells; platelet count >=50 * 10^9/L
                  (without prior platelet transfusion within 7 days before the laboratory test) in
                  subjects in whom >=50% of bone marrow nucleated cells are plasma cells;

               4. Lymphocyte count >=0.3 * 10^9/L;

               5. Aspartate aminotransferase (AST) less than or equal to (<=)3 * upper limit of
                  normal (ULN);

               6. Alanine aminotransferase (ALT) <=3 * ULN;

               7. Total bilirubin <=2.0 * ULN; except in subjects with congenital bilirubinemia,
                  such as Gilbert syndrome (in which case direct bilirubin <=1.5 * ULN is
                  required);

               8. Estimated glomerular filtration rate >=40 milliliter per minute (mL/min) per 1.73
                  meter square (m^2) (to be calculated using the Modification of Diet in Renal
                  Disease [MDRD] formula)

        Exclusion Criteria:

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

          -  Any previous therapy that is targeted to B-cell maturation antigen (BCMA)

          -  Ongoing toxicity from previous anticancer therapy that has not resolved to baseline
             levels or to Grade 1 or less; except for alopecia

          -  Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher
             peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and
             dexamethasone (PVd) as standard therapy or bridging therapy; however, participant may
             receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or
             bridging therapy

          -  Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone
             within the 7 days prior to randomization

          -  Monoclonal antibody treatment within 21 days

          -  Cytotoxic therapy within 14 days

          -  Proteasome inhibitor therapy within 14 days

          -  Immunomodulatory drug (IMiD) therapy within 7 days
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:PFS is defined as the time from the date of randomization to the date of first documented disease progression as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Complete Response (CR) or Stringent Complete Response (sCR) Rate
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:CR or sCR rate is defined as percentage of participants who achieve a CR or sCR response according to the International Myeloma Working Group (IMWG) criteria.
Measure:Overall Minimal Residual Disease (MRD) Negative Rate
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Overall MRD negativity is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.
Measure:MRD Negativity Rate in Participants with CR or sCR at 12 Months +/-3 Months
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:MRD negativity rate in participants with CR or sCR at 12 months +/-3 months is defined as the percentage of participants who achieve MRD-negative status and are in CR or sCR within time window.
Measure:Sustained MRD Negative Rate
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Sustained MRD negativity rate is defined as the percentage of participants who achieve MRD negativity, confirmed minimum 1 year apart and without any examination showing MRD positive status in between.
Measure:Overall Survival (OS)
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:OS is measured from the date of randomization to the date of the participant's death. If the participant is alive or the vital status is unknown, then the participant's data will be censored at the date the participant was last known to be alive.
Measure:Overall response rate (ORR)
Time Frame:Until end of the study (up to 6 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:Time to Worsening of Symptoms
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Time to worsening of symptoms is measured as the interval from the date of randomization to the start date of worsening in the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) total symptom score. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.
Measure:Progression Free Survival on next-line therapy (PFS2)
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.
Measure:Incidence and Severity of Adverse Events (AEs)
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Incidence and severity of AEs will be reported.
Measure:Systemic Cytokine Concentrations
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Serum or plasma proteomic profiling of cytokines (such as interleukin [IL] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.
Measure:Levels of CAR-T Cell Activation Markers
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry or cytometry by time of flight (CyTOF) or both and correlated with response.
Measure:Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
Time Frame:Until end of the study (up to 6 years)
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:Until end of the study (up to 6 years)
Safety Issue:
Description:Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
Measure:Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Measure:Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days" and responses are reported on a 5 point verbal rating scale.
Measure:Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Measure:Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:The PGIS is a single item to assess the subject's perception in the severity of their overall health status using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).
Measure:Frequency in Health-Related Quality of Life as Assessed by The Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item
Time Frame:Until end of the study (up to 6 years)
Safety Issue:
Description:Frequency distributions of the PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the adverse event. A 5-point verbal rating scale is used for subjects to select their experience based on the last 7 days.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

February 5, 2020