1100 Participants Needed

Lenalidomide +/- Daratumumab for Multiple Myeloma

(DRAMMATIC Trial)

Recruiting at 814 trial locations
DS
SH
Tatjana Kolevska, MD, discusses cancer ...
Overseen ByTatjana Kolevska, MD
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: SWOG Cancer Research Network
Must be taking: DVT prophylaxis
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

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.12345

Is 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.45678

What 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.457910

Research Team

Dr. Parameswaran N. Hari, MD ...

Parameswaran Hari, MD

Principal Investigator

Medical College of Wisconsin

AK

Amrita Y. Krishnan

Principal Investigator

City of Hope Medical Center

Eligibility 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

My liver is working well.
I started my initial cancer treatment within the last year and have completed at least two cycles.
I can take and swallow pills whole.
See 17 more

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.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maintenance Treatment

Participants receive Lenalidomide or Lenalidomide + Daratumumab/rHuPH20 for maintenance therapy

2 years
Monthly visits for drug administration

MRD Assessment and Continued Treatment

MRD is assessed to guide further therapy; MRD-positive patients continue treatment, MRD-negative patients are further randomized

Up to 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Treatment Details

Interventions

  • Daratumumab/rHuPH20
  • Lenalidomide
Trial OverviewThe 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.
Participant Groups
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

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials
403
Recruited
267,000+

Southwest Oncology Group

Lead Sponsor

Trials
389
Recruited
260,000+

Janssen, LP

Industry Sponsor

Trials
169
Recruited
329,000+
Founded
1953
Headquarters
Beerse, Belgium
Known For
Mental Health Therapies
Top Products
Imodium, Remicade, Invega, Procrit
Joaquin Duato profile image

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

MBA from ESADE Business School

Biljana Naumovic profile image

Biljana Naumovic

Janssen, LP

Chief Medical Officer since 2023

MD from Belgrade University Medical School

Adaptive

Collaborator

Trials
1
Recruited
1,100+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

The combination therapy of carfilzomib, lenalidomide, dexamethasone, and daratumumab achieved a high minimal residual disease (MRD) negativity rate of 71% in newly diagnosed multiple myeloma patients, indicating effective treatment without the need for high-dose melphalan chemotherapy or autologous transplant.
The treatment demonstrated excellent safety and tolerability, with a 1-year progression-free survival rate of 98% and no reported deaths, although some patients experienced grade 3 or 4 adverse events like neutropenia and rash.
Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial.Landgren, O., Hultcrantz, M., Diamond, B., et al.[2022]
A systematic review of seven randomized controlled trials involving 4268 patients with multiple myeloma showed that combination regimens containing daratumumab significantly improved overall response rates compared to control groups.
While daratumumab enhanced treatment efficacy in both standard-risk and high-risk patients, it was associated with a higher incidence of severe neutropenia and pneumonia, indicating a need for careful monitoring of side effects.
Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis.Wang, Y., Li, Y., Chai, Y.[2021]
In a study of 178 multiple myeloma patients who progressed after daratumumab treatment, the median progression-free survival (PFS) was only 4.5 months and overall survival (OS) was 14.2 months, indicating limited effectiveness of subsequent therapies.
Patients receiving pomalidomide-based therapy had a slightly better median PFS and OS (5.2 months and 21.7 months, respectively) compared to those on carfilzomib-based therapy, highlighting the need for new treatment options for patients previously treated with daratumumab.
Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis.LeBlanc, R., Mian, H., Reece, D., et al.[2023]

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]
Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis. [2021]
Outcome of carfilzomib/pomalidomide-based regimens after daratumumab-based treatment in relapsed multiple myeloma: A Canadian Myeloma Research Group Database analysis. [2023]
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]
Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]
Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]
Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]
Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]
Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. [2021]