Daratumumab-Based Therapy for Multiple Myeloma

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II study of daratumumab based therapies for older adults 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 use other anti-cancer treatments during the study, except for hormonal therapy, which is allowed.

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

Research shows that combining Daratumumab with Bortezomib and Dexamethasone significantly improves patient outcomes in multiple myeloma, with an 80% overall response rate and prolonged progression-free survival compared to standard treatments. This combination has been effective in both newly diagnosed and relapsed/refractory cases, making it a valuable option for patients. ^{1 2 3 4 5}

Is daratumumab-based therapy safe for humans?

Daratumumab-based therapy, when combined with other drugs like lenalidomide, bortezomib, and dexamethasone, has been shown to be generally safe in patients with multiple myeloma. Common side effects include low blood cell counts (neutropenia, thrombocytopenia, anemia) and infections, but these are manageable. ^{1 2 6 7 8}

What makes the drug Daratumumab-Based Therapy for Multiple Myeloma unique?

Daratumumab-Based Therapy is unique because it combines daratumumab, a monoclonal antibody targeting CD38, with bortezomib, lenalidomide, and dexamethasone, which has shown to significantly prolong progression-free survival in multiple myeloma patients compared to standard treatments. This combination offers deep and durable responses, making it a valuable option for relapsed or refractory multiple myeloma. ^{1 5 6 8 9}

Research Team

Rachid C Baz, MD

Principal Investigator

H. Lee Moffitt Cancer & Research Institute

Eligibility Criteria

This trial is for older adults (65+) with newly diagnosed multiple myeloma who haven't had chemotherapy but may have had palliative radiotherapy or a small dose of dexamethasone. They must be able to follow the study schedule, use contraception if necessary, and have adequate organ function and bone marrow capacity. People with severe other illnesses, active infections requiring IV antibiotics, certain viral infections (HIV, hepatitis B/C), or uncontrolled medical conditions are excluded.

Inclusion Criteria

You have high levels of a protein called paraprotein in your blood or urine.

I am over 65 and have health issues that may worsen with intense chemotherapy.

My kidneys are functioning well enough, as per a specific test.

Exclusion Criteria

You have tested positive for hepatitis C.

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

My only sign of plasma cell disorder is a single bone or soft tissue tumor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and dexamethasone for 2 months. Based on response, lenalidomide or bortezomib may be added.

8 weeks

Weekly visits for subcutaneous injections and oral medication

Response Evaluation

Participants are evaluated for response to determine continuation or modification of treatment

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 2 years

Treatment Details

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests daratumumab-based therapies combined with oral dexamethasone, lenalidomide pills, and bortezomib injections in treating multiple myeloma in older adults. It's designed to see how well patients respond to this combination therapy without undergoing high-dose chemotherapy with stem-cell transplantation due to their age or coexisting conditions.

Participant Groups

Group I: C: Daratumumab, Dexamethasone and Bortezomib Experimental Treatment 3 Interventions

Participants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m\^2 Days 1,8 and 15 of each 28 day treatment cycle.

Group II: B: Daratumumab, Dexamethasone and Lenalidomide Experimental Treatment 3 Interventions

Participants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.

Group III: A: Daratumumab & Dexamethasone Experimental Treatment 2 Interventions

All participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.

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

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

In a study of 737 patients with newly diagnosed multiple myeloma, the addition of daratumumab to lenalidomide and dexamethasone significantly reduced the risk of disease progression or death, with a hazard ratio of 0.56, indicating a 44% lower risk compared to the control group.

Patients receiving daratumumab had a higher rate of complete response (47.6% vs. 24.9%) and a greater percentage achieving minimal residual disease status (24.2% vs. 7.3%), although they also experienced more severe side effects like neutropenia and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Facon, T., Kumar, S., Plesner, T., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Daratumumab, a human CD38 monoclonal antibody, shows significant effectiveness in killing multiple myeloma cells that are resistant to lenalidomide and bortezomib, as demonstrated in both ex vivo assays and in vivo mouse models.

The combination of daratumumab with lenalidomide enhances the lysis of resistant myeloma cells and effectively reduces tumor growth in a xenograft model, suggesting a promising new treatment option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib. Nijhof, IS., Groen, RW., Noort, WA., et al.[2020]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

In a study of 162 multiple myeloma patients who received daratumumab, combining it with lenalidomide (DRd) showed no significant difference in progression-free survival (PFS) compared to combining it with pomalidomide (DPd) for those previously treated with lenalidomide.

Both treatment combinations (DRd and DPd) were found to be effective options for patients with relapsed/refractory multiple myeloma, indicating that daratumumab with lenalidomide remains a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. Alhaj Moustafa, M., Parrondo, R., Abdulazeez, MF., et al.[2023]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Daratumumab, Bortezomib, and Dexamethasone versus Bortezomib and Dexamethasone in Chinese Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of LEPUS. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. [2021]