Dara-RVd Induction for Newly Diagnosed Multiple Myeloma With Autologous Stem Cell Transplantation

Phase 2

Suspended

• Conditions: Newly Diagnosed Multiple Myeloma; Multiple Myeloma; Autologous Stem Cell Transplantation
• Interventions: Biological: Daratumumab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

• Registration Number: NCT06348147
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary

This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in subjects with newly diagnosed multiple myeloma (NDMM) who are eligible for standard-of-care autologous stem cell transplantation (ASCT). Daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) have recently become a standard induction regimen for patients with NDMM who are eligible for ASCT in the United States. As implemented in clinical trials, Dara-RVd involves twice weekly bortezomib administration, which is inconvenient for patients and may result in increased rates of limiting toxicity, such as peripheral neuropathy. Adoption of alternate schedules involving once-weekly bortezomib is common in real-world practice, however a paucity of prospective data supporting this practice exists.

This study examines the efficacy of an attenuated Dara-RVd schedule involving once-weekly bortezomib dosing.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-28
• Study First Submitted QC: 2024-03-28
• Study First Posted: 2024-04-04
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-10
• Last Update Posted: 2025-09-11
• Study Start: 2026-01-01
• Primary Completion: 2027-05
• Study Completion: 2029-05-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

1. Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator.
2. Age ≥18 years at the time of consent.
3. Eastern Cooperative Oncology Group (ECOG) ≤ 2
4. Subjects with Multiple Myeloma.

Exclusion Criteria

1. Active infection requiring systemic therapy or other serious infection within 14 days prior to study treatment.
2. Pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Daratumumab, lenalidomide, bortezomib, and dexamethasone	Lenalidomide	Subjects with newly diagnosed multiple myeloma (NDMM) are eligible for standard-of-care autologous stem cell transplantation (ASCT) and receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd).
Daratumumab, lenalidomide, bortezomib, and dexamethasone	Daratumumab	Subjects with newly diagnosed multiple myeloma (NDMM) are eligible for standard-of-care autologous stem cell transplantation (ASCT) and receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd).
Daratumumab, lenalidomide, bortezomib, and dexamethasone	Bortezomib	Subjects with newly diagnosed multiple myeloma (NDMM) are eligible for standard-of-care autologous stem cell transplantation (ASCT) and receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd).
Daratumumab, lenalidomide, bortezomib, and dexamethasone	Dexamethasone	Subjects with newly diagnosed multiple myeloma (NDMM) are eligible for standard-of-care autologous stem cell transplantation (ASCT) and receive daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd).

Primary Outcome Measures

Name	Time	Method
The rate of achievement of bone marrow minimal residual disease (MRD) negativity	At completion of stem cell transplantation (60 days)	The rate of achievement of bone marrow minimal residual disease (MRD) negativity will be defined as the percentage of subjects achieving MRD negativity as determined by next-generation flow cytometry.

Secondary Outcome Measures

Name	Time	Method
Stringent complete response (sCR)	At completion of stem cell transplantation (60 days)	Stringent complete response (sCR) will be defined according to the standard International Myeloma Working Group (IMWG) response criteria for multiple myeloma.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Therapeutic discontinuation	Up to 2 years	Therapeutic discontinuation will be defined as a treatment discontinuation of all drugs for any reason.
Time to best response	Up to 2 years	The time to best response will be defined as the time from the start of study treatment until the time at which a patient's best response according to IMWG criteria is achieved.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Maximum depth of response (from PR to CR, including sCR)	Up to 2 years	The maximum depth of response (from PR to CR, including sCR) will be determined based on IMWG criteria.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Overall response rate (ORR)	Up to 2 years	ORR will be defined as the percentage of subjects achieving a partial response (PR) or better according to IMWG criteria.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Progression Free Survival (PFS )	Up to 2 years	PFS will be defined as the time from the start of study treatment until progression per revised Uniform Response Criteria by the International Myeloma Working Group (IMWG) or death from any cause.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Overall Survival (OS)	Up to 2 years	OS will be defined as the time from the start of treatment to death from any cause.
Time to first response	Up to 2 years	Time to first response will be defined as time from the start of study treatment until the first achievement of at least a partial response (PR) by IMWG criteria or better.; Complete response (CR): Negative immunofixation of serum and urine, the disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.

Trial Locations

Locations (1)

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States