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)

Stichting European Myeloma Network

Status and phase: Enrolling; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Fludarabine; Drug: Daratumumab; Drug: Cilta-cel; Drug: Bortezomib; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Dexamethasone

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT05257083

2021-003284-10 (EudraCT Number)

EMN28/68284528MMY3005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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750 participants in 2 patient groups

Arm A: DVRd + ASCT+DVRd (Standard Therapy)

Active Comparator group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Lenalidomide

Drug: Bortezomib

Drug: Daratumumab

Arm B: DVRd followed by Ciltacabtagene Autoleucel

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Cyclophosphamide

Drug: Lenalidomide

Drug: Bortezomib

Drug: Cilta-cel

Drug: Daratumumab

Drug: Fludarabine