Phase 2 Study With Minimal Residual Disease (MRD) Driven Adaptive Strategy in Treatment for Newly Diagnosed Multiple Myeloma (MM) With Upfront Daratumumab-based Therapy
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04140162
- Lead Sponsor
- University of Michigan Rogel Cancer Center
- Brief Summary
This phase 2 trial will test whether the combination of DaraRd (daratumumab + lenalidomide + dexamethasone) as induction therapy, followed by DRVd (daratumumab + lenalidomide + bortezomib + dexamethasone) consolidation therapy, if needed, will result in more patients achieving minimal residual disease (MRD)-negative status, relative to the standard of care. Consolidation therapy will be administered only to those patients with MRD-positive status after induction therapy.
This is a study based on adaptive design for decision making of treatment options. Duration of therapy (daratumumab cycles) will depend on individual approach, response, evidence of disease progression and tolerance.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 57
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dara-Rd followed by Dara-RVd Daratumumab * Induction regimen with Daratumumab, Lenalidomide and Dexamethasone (Dara-Rd) in all study subjects, weeks 1-24 * Consolidation regimen with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (Dara-RVd) in post-induction MRD+ population, weeks 25-36 * Maintenance regimen with Daratumumab and Lenalidomide (Dara-R) in all study subjects, weeks 37-88 * Maintenance regimen with lenalidomide (R) until progression or intolerance Dara-Rd followed by Dara-RVd Lenalidomide * Induction regimen with Daratumumab, Lenalidomide and Dexamethasone (Dara-Rd) in all study subjects, weeks 1-24 * Consolidation regimen with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (Dara-RVd) in post-induction MRD+ population, weeks 25-36 * Maintenance regimen with Daratumumab and Lenalidomide (Dara-R) in all study subjects, weeks 37-88 * Maintenance regimen with lenalidomide (R) until progression or intolerance Dara-Rd followed by Dara-RVd Bortezomib * Induction regimen with Daratumumab, Lenalidomide and Dexamethasone (Dara-Rd) in all study subjects, weeks 1-24 * Consolidation regimen with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (Dara-RVd) in post-induction MRD+ population, weeks 25-36 * Maintenance regimen with Daratumumab and Lenalidomide (Dara-R) in all study subjects, weeks 37-88 * Maintenance regimen with lenalidomide (R) until progression or intolerance Dara-Rd followed by Dara-RVd Dexamethasone * Induction regimen with Daratumumab, Lenalidomide and Dexamethasone (Dara-Rd) in all study subjects, weeks 1-24 * Consolidation regimen with Daratumumab, Lenalidomide, Bortezomib and Dexamethasone (Dara-RVd) in post-induction MRD+ population, weeks 25-36 * Maintenance regimen with Daratumumab and Lenalidomide (Dara-R) in all study subjects, weeks 37-88 * Maintenance regimen with lenalidomide (R) until progression or intolerance
- Primary Outcome Measures
Name Time Method Proportion of participants who achieve MRD negativity either after induction or, if still MRD-positive after induction, after consolidation. At the end of week 36 (post-consolidation therapy) Of participants who complete at least one cycle of induction therapy, proportion that achieve MRD-negativity after completion of induction + those who achieve MRD-negativity after completion of consolidation (if still MRD-positive after induction). MRD status determined by International Myeloma Working Group (IMWG) Response Criteria.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to 3 years after start of study treatment Time from initiation of daratumumab-based combination regimen until death or last follow-up date (whichever occurs first).
Progression-free Survival (PFS) Up to 3 years after start of study treatment Time from initiation of daratumumab-based combination regimen to disease progression, where disease progression is according to the IMWG criteria, death, or last disease evaluation before the start of any subsequent anti-myeloma therapy (whichever occurs first).
Proportion of participants who were MRD-positive after induction and subsequently achieve MRD-negative after consolidation. At the end of week 36 (post-consolidation therapy) Of participants who are still MRD-positive after induction, proportion that achieve MRD-negative after consolidation. Per IMWG Response Criteria
Health-related quality of life assessment changes from baseline using EuroQol survey "EQ-5D." Baseline to 16 weeks post-last-dose of study treatment (Dara, R, V or d) EQ-5D is a standardized participant-reported outcome measure developed by the EuroQol Group and used in this trial to assess health-related quality of life.
Incidence of treatment-emergent adverse events From start of study treatment (Dara-Rd) up to 30 days post last dose of study treatment (Dara, R, V or d) Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Proportion of participants who maintain post-induction MRD-negativity to post-consolidation At the end of week 36 (post-consolidation therapy) Of participants who achieve post-induction MRD-negativity, proportion that maintain MRD-negativity through completion of consolidation therapy.
Proportion of participants who maintain post-induction MRD-negativity to post-consolidation. At the end of week 88 (post 1 year of maintenance therapy) Of participants who achieve post-induction MRD-negativity, proportion that maintain MRD-negativity through completion of 1 year of maintenance therapy.
Proportion of participants who maintain post-induction MRD-negativity to last follow-up visit. After week 88, up to 3 years after start of study treatment Of participants who achieve post-induction MRD-negativity, proportion that maintain MRD-negativity until last follow-up visit (if after week 88).
Neurotoxicity assessment changes from baseline using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. Baseline to 16 weeks post-last-dose of study treatment (Dara, R, V or d) The FACT/GOG-Ntx is a patient-reported outcome measure used to assess health-related quality of life in patients undergoing cancer therapy, plus an eleven-item subscale (Ntx subscale) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy.
Proportion of participants with a successful stem cell mobilization after receiving Dara-based induction therapy. At the end of week 24 (post-induction therapy) Of participants who have stem cells collected, proportion who have enough CD34+ cells after mobilization to be able to proceed with an autologous stem cell transplant (ASCT) if needed. Successful mobilization for each participant will be based on standard criteria at the institution where the transplant will be administered.
Trial Locations
- Locations (4)
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
University of Texas Southwestern -- Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
University of Rochester
🇺🇸Rochester, New York, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States