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Purpose

The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.

Condition

Eligibility

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

Inclusion Criteria

  • Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan. - Measurable disease, as assessed by central laboratory, at screening as defined by any of the following: 1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or 2. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. - ECOG performance status of grade 0 or 1 - Clinical laboratory values within prespecified range.

Exclusion Criteria

  • Prior treatment with CAR-T therapy directed at any target. - Any prior BCMA target therapy. - Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids - Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization - Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization. - Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM - Stroke or seizure within 6 months of signing Informed Consent Form (ICF)

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
Active Comparator
Arm A: DVRd + ASCT+DVRd (Standard Therapy) 		Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
  • Drug: Daratumumab
    Daratumumab will be administered SC.
  • Drug: Bortezomib
    Bortezomib will be administered SC.
  • Drug: Lenalidomide
    Lenalidomide will be administered orally.
  • Drug: Dexamethasone
    Dexamethasone will be administered orally.
Experimental
Arm B: DVRd followed by Ciltacabtagene Autoleucel 		Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles. Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist of 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
  • Drug: Daratumumab
    Daratumumab will be administered SC.
  • Drug: Bortezomib
    Bortezomib will be administered SC.
  • Drug: Lenalidomide
    Lenalidomide will be administered orally.
  • Drug: Dexamethasone
    Dexamethasone will be administered orally.
  • Drug: Cilta-cel
    Cilta-cel will be administered intravenously
    Other names:
    • JNJ-68284528
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered intravenously.
  • Drug: Fludarabine
    Fludarabine will be administered intravenously.

Recruiting Locations

University of Arkansas
Little Rock, Arkansas 72205
Contact:
Van Rhee

City of Hope
Duarte, California 91010
Contact:
Htut

UC San Diego Health Moores Cancer Center
San Diego, California 92037
Contact:
Costello

University of California San Francisco (UCSF)
San Francisco, California 94143
Contact:
Chung

Stanford University
Stanford, California 94305
Contact:
Sidana

Moffitt Cancer Center
Tampa, Florida 12902
Contact:
Castaneda Puglianini

University of Chicago
Chicago, Illinois 60637
Contact:
Jakubowiak

University of Iowa
Iowa City, Iowa 52242
Contact:
Strouse

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Petrocca

Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Contact:
Anderson

Montefiore M-E Center
Bronx, New York 10461
Contact:
Shah

Mount Sinai Medical Venter
New York, New York 10029
Contact:
Rossi

Levine Cancer Institute
Charlotte, North Carolina 28204
Contact:
Voorhees

The Ohio State University
Columbus, Ohio 43210
Contact:
Khan

Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
Contact:
Gergis

University of Texas Southwestern Medical Center
Dallas, Texas 75390
Contact:
Anderson

University of Virginia
Charlottesville, Virginia 22903
Contact:
Foster

More Details

NCT ID
NCT05257083
Status
Recruiting
Sponsor
Stichting European Myeloma Network

Study Contact

Giulia Gazzera
+39 377 390 9394
giulia.gazzera@emn.org

Detailed Description

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT). Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.

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.