A Study 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 Participants With Newly Diagnosed Multiple Myeloma (CARTITUDE-6)
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- Full Title:
- A Phase 3 Randomized Study Comparing 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 Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible
- Myeloma stage or condition:
- Multiple Myeloma
- Study phase:
- Phase 3
- Summary/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.
- 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.
- Treatments:
- 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
- Drug : Cyclophosphamide
Cyclophosphamide will be administered intravenously.
- Drug : Fludarabine
Fludarabine will be administered intravenously.
- Study Arms:
- 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 - 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
- Study Type:
- Interventional
- Study Design:
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: None (Open Label)
- Recruitment status:
- Recruiting
- Eligibility criteria:
-
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.
- 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)
- Locations / Centres:
-
Tom Baker Cancer Center, Calgary, – Not yet recruiting
Cross Cancer Institute, Edmonton, – Not yet recruiting
McMaster University, Hamilton, – Recruiting
Hopital Maisonneuve-Rosemont, Montréal, – Not yet recruiting
Mcgill University Health Centre, Montréal, – Not yet recruiting
Ottawa Hospital Research Institute, Ottawa, – Not yet recruiting
(CHU) Centre Hospitalier Universitaire de Quebec Laval, Québec, – Not yet recruiting
Princess Margaret Cancer Centre, Toronto, – Not yet recruiting
Vancouver General Hospital, Vancouver, – Not yet recruiting
- Contacts:
- Name: Sarah Lonergan
Phone: +31 107033123
Email: [email protected]
- Publications:
- ???
- First posted:
- 2022-02-25
- Actual start date:
- October 10, 2023
- Last updated:
- 2024-05-14
- Estimated enrollment:
- 750
- Estimated completion date:
- 2040-08-01
- Estimated primary completion date:
- 2033-06-01
- Condition:
- Multiple Myeloma
- Gender:
- All
- Ages:
- 18 Years-N/A
- Accepts healthy volunteers:
- No
- Listed location countries:
- Australia
- Belgium
- Canada
- Czechia
- France
- Germany
- Greece
- Israel
- Italy
- Japan
- Netherlands
- Norway
- Spain
- Sweden
- Switzerland
- United Kingdom
- United States
- NCT number:
- NCT05257083
- Other study ID numbers:
- EMN28/68284528MMY3005
- Has Data monitoring committee:
- Yes
- U.S. FDA-regulated product:
- Yes
- IPD Sharing Statement :
- ???
- Responsible party:
-
Sponsor
- Study sponsor:
- collaborator
Janssen Research & Development, LLC
Industry - lead_sponsor
Stichting European Myeloma Network
Other
- Collaborators:
- ???
- Investigators:
- Not available
- Protocol Registration and Results System:
- ???
- Verification date:
- 2024-05-01