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

Multiple Myeloma Clinical Trial

Official title:

An Attenuated Schedule Dara-RVd Induction for Patients With Newly Diagnosed Multiple Myeloma Who Are Eligible for Autologous Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06348147
• Other study ID #: LCCC2323
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2024
• Est. completion date: August 2028

Study information

• Verified date: April 2024
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: Ralph L Dessieu
• Phone: 919-966-3066
• Email: Ralph-Lyne_Dessieu[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 39
• Est. completion date: August 2028
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Autologous Stem Cell Transplantation
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Newly Diagnosed Multiple Myeloma

Intervention

Biological:
• Daratumumab
Daratumumab is a CD38-directed cytolytic antibody indicated for the treatment of adults with multiple myeloma. 1800 mg will be given subcutaneously according to its standard package insert schedule.

Drug:
• Lenalidomide
Lenalidomide will be administered, once daily orally on Days 1-21 of a 28-day
• Bortezomib
Bortezomib is a proteasome inhibitor indicated for the treatment of adult patients with multiple myeloma, will be given subcutaneously once weekly on days 1, 8, and 15 of every 28 day cycle.
• Dexamethasone
Dexamethasone is a glucocorticoid.

Locations

Country	Name	City	State
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of achievement of bone marrow minimal residual disease (MRD) negativity	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.	At completion of stem cell transplantation (60 days)
Secondary	Progression Free Survival (PFS )	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.	Up to 2 years
Secondary	Stringent complete response (sCR)	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.	At completion of stem cell transplantation (60 days)
Secondary	Overall Survival (OS)	OS will be defined as the time from the start of treatment to death from any cause.	Up to 2 years
Secondary	Therapeutic discontinuation	Therapeutic discontinuation will be defined as a treatment discontinuation of all drugs for any reason.	Up to 2 years
Secondary	Time to first response	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.	Up to 2 years
Secondary	Time to best response	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.	Up to 2 years
Secondary	Maximum depth of response (from PR to CR, including sCR)	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.	Up to 2 years
Secondary	Overall response rate (ORR)	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.	Up to 2 years

External Links

•   University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials