49 Participants Needed

Daratumumab-Based Regimens for Multiple Myeloma

(DeRIVE Trial)

AN
Overseen ByAjay Nooka, MD, MPH
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well daratumumab, ixazomib, and dexamethasone with or without bortezomib work in treating patients with newly diagnosed multiple myeloma. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as ixazomib, dexamethasone, and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving daratumumab, ixazomib, and dexamethasone with or without bortezomib may work better in treating patients with multiple myeloma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong CYP3A inducers (e.g., rifampin, carbamazepine) within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of Daratumumab, Bortezomib, and Dexamethasone for treating multiple myeloma?

Research shows that adding Daratumumab to Bortezomib and Dexamethasone significantly improves patient outcomes in multiple myeloma, including longer periods without disease progression and higher response rates compared to using Bortezomib and Dexamethasone alone. This combination has been effective in both newly diagnosed and relapsed cases of multiple myeloma.12345

Is daratumumab-based treatment safe for humans?

Daratumumab-based treatments, including combinations with bortezomib and dexamethasone, have been shown to be generally safe for humans. Common side effects include infusion-related reactions, neutropenia (low white blood cell count), thrombocytopenia (low platelet count), anemia (low red blood cell count), and infections, but these are typically manageable.12467

What makes the drug combination of Bortezomib, Daratumumab, Dexamethasone, and Ixazomib unique for treating multiple myeloma?

This drug combination is unique because it includes Daratumumab, a first-in-class monoclonal antibody that targets CD38 on multiple myeloma cells, enhancing the immune system's ability to kill these cancer cells. Additionally, the combination of these drugs offers a novel approach by integrating different mechanisms of action, potentially improving outcomes for patients who have relapsed or are resistant to other treatments.1891011

Research Team

Ajay K. Nooka, MD, MPH, FACP | Winship ...

Ajay K. Nooka, MD,MPH,FACP

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who are in good physical condition (ECOG PS 0-1) and have measurable disease. They can't have had certain other conditions or treatments, must agree to contraception if applicable, and be willing to follow the study rules. Pregnant women, those with allergies to study drugs, or patients treated previously with similar drugs are excluded.

Inclusion Criteria

I agree to use contraception as required.
I am fully active or restricted in physically strenuous activity but can do light work.
You have a certain level of M-protein in your blood or urine that can be measured.
See 8 more

Exclusion Criteria

I haven't taken strong CYP3A inducers or St. John's wort recently.
I am allergic or react badly to dexamethasone, boron, mannitol, or similar drugs.
I have been treated with anti-CD38 therapy before.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive dexamethasone, daratumumab, and either ixazomib or bortezomib in cycles to treat multiple myeloma

24 weeks
Weekly visits for drug administration

Stem Cell Transplant

Eligible patients undergo stem cell transplant per standard of care

4 weeks

Maintenance

Patients continue treatment with dexamethasone, daratumumab, and ixazomib for up to 24 months

24 months
Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for up to 5 years

Treatment Details

Interventions

  • Bortezomib
  • Daratumumab
  • Dexamethasone
  • Ixazomib
Trial OverviewThe trial is testing a combination of daratumumab, ixazomib, and dexamethasone against the same combo plus bortezomib in treating new multiple myeloma cases. It aims to see which regimen is more effective at stopping cancer growth by comparing these two treatment groups.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (DVd, DId)Experimental Treatment4 Interventions
INDUCTION CYCLES 1-3: Patients receive dexamethasone IV and PO on days 1, 8, and 15, daratumumab IV on days 1, 8, and 15, and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. INDUCTION CYCLES 4-8: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1 and 15, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV on day 1, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (DId)Experimental Treatment3 Interventions
INDUCTION: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-8, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Velcade for:
  • Multiple myeloma
  • Mantle cell lymphoma
🇺🇸
Approved in United States as Velcade for:
  • Multiple myeloma
  • Mantle cell lymphoma
🇨🇦
Approved in Canada as Velcade for:
  • Multiple myeloma
  • Mantle cell lymphoma
🇯🇵
Approved in Japan as Velcade for:
  • Multiple myeloma
  • Mantle cell lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials
1,735
Recruited
2,605,000+

Takeda

Industry Sponsor

Trials
1,255
Recruited
4,219,000+
Dr. Naoyoshi Hirota profile image

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber profile image

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

National Institutes of Health (NIH)

Collaborator

Trials
2,896
Recruited
8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

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

Findings from Research

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.
The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.
Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma.Lamb, YN.[2021]
In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.
Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.
Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]
In the phase 3 LEPUS study involving 211 Chinese patients with relapsed or refractory multiple myeloma, the combination of daratumumab, bortezomib, and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) compared to bortezomib and dexamethasone alone (median PFS of 14.8 months vs. 6.3 months).
D-Vd also showed higher overall response rates and better response quality, with 84.7% of patients achieving an overall response compared to 66.7% with Vd, and no new safety concerns were identified, supporting D-Vd as a standard treatment option.
Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS.Fu, W., Li, W., Hu, J., et al.[2023]

References

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]
Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. [2019]
Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. [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]
Daratumumab for the treatment of multiple myeloma. [2018]
Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. [2019]
Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma. [2023]
Daratumumab and its use in the treatment of relapsed and/or refractory multiple myeloma. [2020]
Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]
Daratumumab: First Global Approval. [2018]