Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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): 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 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; 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 participants 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, 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A: PVd or DPd (Standard Therapy)
Participants 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.
  • Drug: Pomalidomide
    Pomalidomide 4 mg will be administered orally.
  • Drug: Bortezomib
    Bortezomib 1.3 milligram per meter square (mg/m^2) will be administered subcutaneously (SC).
  • Drug: Dexamethasone
    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.
  • Drug: Daratumumab
    Daratumumab 1800 mg will be administered SC.
Experimental
Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel])
Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of JNJ-68284528 (cilta-cel) 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 (cilta-cel) infusion 0.75 * 10^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg).
  • Drug: JNJ-68284528
    Cilta-cel infusion will be administered at a target dose of 0.75 * 10^6 CAR-positive viable T cells/kilogram (kg).
    Other names:
    • Cilta-cel

Recruiting Locations

University of Kansas
Westwood, Kansas 66205

More Details

Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

Study Contact
844-434-4210
JNJ.CT@sylogent.com

Detailed Description

Multiple myeloma is a malignant plasma cell disorder diagnosed annually in approximately 86,000 participants worldwide. JNJ-68284528 (cilta-cel) 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 (cilta-cel) 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 data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 6 years.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.