Lenalidomide +/- Daratumumab for Multiple Myeloma (DRAMMATIC Trial)
Recruiting in Palo Alto (17 mi)
+814 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: SWOG Cancer Research Network
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg and followed for up to 15 years.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, you must not have received any investigational agents within 14 days prior to registration, and you must be able to take DVT prophylaxis (blood clot prevention medication).
What data supports the effectiveness of the drug combination Lenalidomide and Daratumumab for treating multiple myeloma?
Research shows that adding daratumumab to lenalidomide and dexamethasone significantly improves outcomes for patients with multiple myeloma, including longer periods without disease progression and higher overall survival rates. In one study, the combination had an 80% response rate, indicating it is effective in treating this condition.
12345Is the combination of Lenalidomide and Daratumumab safe for treating multiple myeloma?
The combination of Lenalidomide and Daratumumab has been studied in multiple myeloma patients and is generally considered safe. Common side effects include low blood cell counts (neutropenia, thrombocytopenia, anemia), nerve damage (peripheral sensory neuropathy), and infections. Infusion-related reactions, mostly mild, can occur, especially during the first treatment.
45678What makes the drug Lenalidomide combined with Daratumumab unique for treating multiple myeloma?
This drug combination is unique because it pairs lenalidomide, an immunomodulatory drug, with daratumumab, a monoclonal antibody that targets CD38 on myeloma cells, enhancing the immune system's ability to kill these cancer cells. This combination has shown to improve progression-free survival and overall response rates in patients with multiple myeloma.
457910Eligibility Criteria
This trial is for adults aged 18-75 with symptomatic multiple myeloma who've had induction therapy and a stem cell transplant within the last year. They must be able to take oral meds, have good kidney and liver function, no severe lung issues or uncontrolled infections, and not allergic to study drugs. HIV-positive patients can join if their viral load is undetectable.Inclusion Criteria
I can take and swallow pills whole.
I have multiple myeloma and received treatment before a stem cell transplant.
I was diagnosed with multiple myeloma and received treatment before a stem cell transplant.
I started my initial cancer treatment within the last year and have completed at least two cycles.
I have HIV, am on treatment, and my viral load is undetectable.
I am between 18 and 75 years old.
I can take care of myself but might not be able to do heavy physical work.
Exclusion Criteria
I haven't had severe asthma in the last 2 years and my asthma is currently under control.
My multiple myeloma has not spread to my brain or spinal cord.
My cancer has not worsened before signing up for this trial.
I do not have any ongoing serious infections.
My multiple myeloma does not only produce non-detectable levels of proteins in blood and urine.
I have not had any organ transplants or bone marrow transplants.
I can tolerate lenalidomide and daratumumab treatments.
I have not failed to respond to treatments with lenalidomide or daratumumab.
I do not have any severe illnesses that are not under control.
My lung function is more than half of what is expected for someone my age and size.
I do not have smoldering myeloma.
I have not had any other types of cancer before.
My organs are not affected by amyloidosis.
Participant Groups
The trial tests Lenalidomide alone versus Lenalidomide plus Daratumumab/rHuPH20 as maintenance therapy post-autologous stem cell transplant (ASCT) in multiple myeloma patients. It uses MRD status after two years of treatment to decide further therapy duration, with possible treatment up to seven years.
7Treatment groups
Experimental Treatment
Active Control
Group I: Arm 2: Lenalidomide + Daratumumab/rHuPH20Experimental Treatment2 Interventions
Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 2 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 2 years from starting treatment.
Group II: Arm 2b: Stop Lenalidomide + Daratumumab/rHuPH20Active Control1 Intervention
MRD- and randomized to Arm 2b: Discontinue protocol therapy.
Group III: Arm 1a: Continue LenalidomideActive Control1 Intervention
MRD+ or MRD- and randomized to Arm 1a: Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 7 years from starting treatment.
Group IV: Arm 1b: Stop LenalidomideActive Control1 Intervention
MRD- and randomized to Arm 1b: Discontinue protocol therapy.
Group V: Study Entry / ScreeningActive Control1 Intervention
Study entry/screening to follow patient until Maintenance.
Group VI: Arm 1: LenalidomideActive Control1 Intervention
Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 2 years from starting treatment.
Group VII: Arm 2a: Continue Lenalidomide + Daratumumab/rHuPH20Active Control2 Interventions
MRD+ or MRD- and randomized to Arm 2a: Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 7 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 7 years from starting treatment.
Lenalidomide is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Revlimid for:
- Multiple myeloma
- Myelodysplastic syndromes
- Mantle cell lymphoma
- Follicular lymphoma
- Marginal zone lymphoma
🇺🇸 Approved in United States as Revlimid for:
- Multiple myeloma
- Myelodysplastic syndromes
- Mantle cell lymphoma
- Follicular lymphoma
- Marginal zone lymphoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Mercy Health Mercy CampusMuskegon, MI
Mercy Cancer Center - SacramentoSacramento, CA
UM Sylvester Comprehensive Cancer Center at PlantationPlantation, FL
Saint Anthony's HealthAlton, IL
More Trial Locations
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Who is running the clinical trial?
SWOG Cancer Research NetworkLead Sponsor
Southwest Oncology GroupLead Sponsor
Janssen, LPIndustry Sponsor
AdaptiveCollaborator
National Cancer Institute (NCI)Collaborator
References
Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. [2022]Recently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone.
Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis. [2021]To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM).
Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. [2023]Although daratumumab-containing regimens improve multiple myeloma (MM) outcomes, recurrence is inevitable.
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.
Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]The multiple myeloma (MM) treatment has changed over the last years due to the introduction of novel drugs. Despite improvements in the MM outcome, MM remains an incurable disease. Daratumumab is a human IgGK monoclonal antibody targeting CD38 with tumor activity associated with immunomodulatory mechanism. In combination with standard of care regimens, including bortezomib (Vd) or lenalidomide (Rd), daratumumab prolonged progression-free survival (PFS) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) and in new diagnosis MM. We report the data of the MM GIMEMA Lazio group in 171 heavily treated pts who received daratumumab, lenalidomide and dexamethasone (DRd) or daratumumab, velcade and dexamethasone (DVd). The overall response rate was 80%, and the overall survival (OS) and PFS were 84% and 77%, respectively. In addition, pts treated with DRd showed a better median PFS compared to pts treated with DVd, at 12 and 24 months, respectively. The most common hematologic treatment-emergent adverse events (TAEs) were neutropenia, thrombocytopenia, and anemia. The most common nonhematologic TAEs were peripheral sensory neuropathy and infections. Our data confirmed that DRd or DVd therapy is effective and safe in RRMM pts, and our real-life analysis could support the physicians regarding the choice of optimal therapy in this setting of pts.
Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P<0.0001). The overall response rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response or better, respectively (both P<0.0001). At the 10-5 sensitivity threshold, 26.2% versus 6.4% were minimal residual disease-negative, respectively (P<0.0001). Post hoc analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P<0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 vs 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P=0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone. Trial Registration: clinicaltrials.gov identifier: 02076009.
Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029.
Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]To review the available data for the efficacy and safety of daratumumab in the treatment of multiple myeloma (MM), both in the newly diagnosed and relapsed/refractory settings, as well as provide additional guidance to clinicians on operational, safety, and supportive care considerations.
Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. [2021]In our efforts to develop novel effective treatment regimens for multiple myeloma we evaluated the potential benefits of combining the immunomodulatory drug lenalidomide with daratumumab. Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.