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NCT Number: NCT04181827

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

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Royal Adelaide Hospital, Adelaide, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 (>=) 0.5 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 (failure to achieve minimal response or 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. However, participants must be refractory to lenalidomide in at least one prior line
  • 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):
  • Hemoglobin >=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
  • 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);
  • Platelet count >=75 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants 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 participants in whom >=50% of bone marrow nucleated cells are plasma cells;
  • Lymphocyte count >=0.3 * 10^9/L;
  • Aspartate aminotransferase (AST) less than or equal to (<=)3 * upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) <=3 * ULN;
  • Total bilirubin <=2.0 * ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5 * ULN is required);
  • 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, participants 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

Treatment and study plan

Cilta-cel

Drug

Cilta-cel infusion will be administered at a target dose of 0.75 * 10^6 CAR-positive viable T cells/kilogram (kg).

Pomalidomide

Drug

Pomalidomide 4 mg will be administered orally.

bortezomib

Drug

Bortezomib 1.3 milligram per meter square (mg/m^2) will be administered subcutaneously (SC).

Dexamethasone

Drug

Dexamethasone 20 mg/day (10mg/day for participants >75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants >75 years of age) in DPd treatment.

Daratumumab

Drug

Daratumumab 1800 mg will be administered SC.

Primary outcomes

  1. Progression Free Survival (PFS)

    Time frame: From randomization (Day 1) to either progressive disease or death, whichever occurred first (up to 3.9 years)

    PFS: defined as time from date of randomization to date of first documented progressed disease (PD) as per International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurred first. PD: increase of 25% from lowest response value: serum and urine M-component (absolute increase must be >=0.5 grams per deciliter [g/dL] and >=200 milligrams [mg] per 24 hours, respectively); only in participants without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase of >10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell (PC)% (absolute increase of >=10%), appearance of new lesion; definite development of new bone lesions or definite increase in size of existing bone lesions, >=50% increase in circulating PCs (minimum of 200 cells per microliter [uL]) if this was only measure of disease.

Secondary outcomes

  1. Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR)

    Time frame: From randomization (Day 1) up to 7 years

  2. Percentage of Participants Who Achieved Overall Minimal Residual Disease (MRD) Negative Status (at 10^-5)

    Time frame: From randomization (Day 1) up to 7 years

  3. Percentage of Participants Who Were in CR or sCR and Achieved MRD-negative Status at 12 Months +/-3 Months

    Time frame: From randomization (Day 1) up to 12 months +/- 3 months

  4. Percentage of Participants Who Achieved Sustained MRD-negative Status

    Time frame: From randomization (Day 1) up to 7 years

  5. Overall Survival (OS)

    Time frame: From randomization (Day 1) up to 7 years

  6. Time to Worsening of Symptoms Using the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Total Symptom Score

    Time frame: From randomization (Day 1) up to 7 years

  7. Overall Response Rate (ORR)

    Time frame: From randomization (Day 1) up to 7 years

  8. Progression Free Survival on Next-line Therapy (PFS2)

    Time frame: From randomization (Day 1) up to 7 years

  9. Number of Participants With Treatment-emergent Adverse Events (AEs)

    Time frame: From Cycle 1 Day 1 up to 7 years

  10. Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity

    Time frame: From Cycle 1 Day 1 up to 7 years

  11. Change From Baseline in Systemic Cytokine Concentrations on Participants Who Received Cilta-cel as Study Treatment (Arm B)

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years

  12. Change From Baseline in Levels of CAR-T Cell Activation Markers on Participants Who Received Cilta-cel as Study Treatment (Arm B)

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  13. Change From Baseline in Levels of JNJ-68284528 T Cell Expansion (Proliferation), and Persistence on Participants Who Received Cilta-cel as Study Treatment (Arm B)

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  14. Number of Participants With Anti-JNJ-68284528 Antibodies on Participants Who Received Cilta-cel as Study Treatment (Arm B)

    Time frame: From Cycle 1 Day 1 up to 7 years

  15. Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 Item (EORTC-QLQ-C30) Scale Score

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  16. Change From Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  17. Change From Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Scale Score

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  18. Change From Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score

    Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)

  19. Number of Participants 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: From randomization (Day 1) up to 7 years

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study 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

Acronym: CARTITUDE-4

Important dates

Study start
2020
Primary completion
2024
Study completion
2027
First posted
Dec 2, 2019
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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