A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

Official Title

A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

Summary:

The purpose of this study to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.

Trial Description

Primary Outcome:

  • Percentage of Participants with Negative Minimal Residual Disease (MRD) Status
Secondary Outcome:
  • Progression-Free Survival (PFS)
  • MRD Negative Rate at 1 Year
  • Durable MRD Negative Rate
  • Overall Response Rate (ORR)
  • Very Good Partial Response (VGPR) or Better Rate
  • Complete Response (CR) or Better Rate
  • PFS on the Next Line of Therapy
  • Overall Survival (OS)
  • Time to Response
  • Duration of Response (DOR)
  • Change from Baseline in Health-related Quality of Life (HRQoL) using EORTC Questionnaires
  • Change from Baseline in Health-related Quality of Life (HRQoL) using EQ-5D-5L Questionnaire
  • Maximum Observed Serum Concentration (Cmax) of Daratumumab
  • Minimum Observed Serum Concentration (Cmin) of Daratumumab
  • Number of Participants with Anit-daratumumab Antibodies
  • Number of Participants with Anit-rHuPH20 Antibodies
This study will evaluate participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. The data available from other available studies suggests that addition of daratumumab with Velcade (bortezomib), lenalidomide, and dexamethasone [VRd] is anticipated to improve the response rates and the depth of response and may lead to improved long-term outcomes in newly diagnosed participants with MM. Daratumumab targets CD38, a protein expressed on the surface of MM cells and other hematopoietic cells. Bortezomib is a proteasome inhibitor, which plays a critical role in the pathogenesis of MM. Lenalidomide has cytotoxic effects on myeloma cells and is capable of inducing apoptosis, or programmed cell death and dexamethasone induces apoptosis in MM cells. The rationale for the study is to utilize the subcutaneous (SC) formulation of daratumumab instead of the intravenous (IV) formulation, which is expected to provide similar exposure and is expected to limit additional toxicity to participants, treated with this quadruplet regimen. The study will consist of 3 phases: Screening (up to 28 days before randomization), Treatment phase (from Cycle 1 [21 days] Day 1 and continues until disease progression) and Follow up (Postintervention). Efficacy evaluations will include measurements of tumour burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. Participants will undergo procedures like electrocardiogram (ECG), chest x-rays or full dose chest CT scans, Pulmonary function test (PFT), spirometry etc. during the course of study. Participants will also be monitored closely for adverse events (AEs), laboratory abnormalities, and clinical response. The duration of the study will be approximately 6.5 years.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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