Daratumumab + Lenalidomide for Multiple Myeloma

Overseen By Jessica Ellis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must not be taking: Cancer therapy

Disqualifiers: Primary amyloidosis, Waldenström's, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks for initial treatment cycles, followed by ongoing treatment

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests two medications, daratumumab and lenalidomide, for treating multiple myeloma without using steroids. It focuses on patients who cannot have a transplant. Daratumumab helps the immune system destroy cancer cells, and lenalidomide boosts the immune system and stops cancer growth.

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, if you are receiving cancer therapy or have had radiation therapy recently, you may not be eligible to participate.

What data supports the effectiveness of the drug Daratumumab combined with Lenalidomide for Multiple Myeloma?

Research shows that adding Daratumumab to Lenalidomide and Dexamethasone significantly reduces the risk of disease progression or death in patients with relapsed or refractory multiple myeloma. In one study, this combination improved progression-free survival and increased the overall response rate compared to Lenalidomide and Dexamethasone alone. ^{1 2 3 4 5}

Is the combination of Daratumumab and Lenalidomide safe for humans?

The Phase III MAIA trial evaluated the combination of daratumumab and lenalidomide in patients with multiple myeloma and provided safety data, indicating it is generally safe for human use. ^{6 7 8 9 10}

What makes the drug combination of Daratumumab and Lenalidomide unique for treating multiple myeloma?

The combination of Daratumumab and Lenalidomide is unique because Daratumumab is a monoclonal antibody that targets CD38 on multiple myeloma cells, enhancing their destruction through various immune mechanisms, while Lenalidomide modulates the immune system to further support this process, making the combination particularly effective in prolonging progression-free survival in patients. ^{2 4 11 12 13}

Research Team

Frank Passero, MD

Principal Investigator

University of Rochester

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who haven't had previous treatments and can't have a transplant. They should be able to take oral meds, not be pregnant or breastfeeding, and must not have other severe health issues or recent major surgeries.

Inclusion Criteria

I can take care of myself but cannot do any physical work.

I am a woman who cannot become pregnant because I am either surgically sterile or post-menopausal.

My organs are functioning well.

Exclusion Criteria

I have been diagnosed with a specific blood disorder but it's not active cancer.

I have been diagnosed with Waldenström's disease.

I was diagnosed with cancer less than 2 years ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, lenalidomide, and dexamethasone. Daratumumab is administered weekly for 8 treatments, then every 2 weeks for 8 treatments, followed by every 4 weeks. Lenalidomide is given daily on days 1-21 of a 28-day cycle.

16 weeks for initial treatment cycles, followed by ongoing treatment

Weekly visits initially, then bi-weekly, then monthly

Response Assessment

Response assessments by International Myeloma Working Group criteria for myeloma will be performed every 4 weeks while on therapy.

Ongoing during treatment

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Daratumumab
• Lenalidomide

Trial Overview The study tests the effectiveness of daratumumab and lenalidomide without steroids in treating multiple myeloma. It aims to see if patients can avoid steroid-related side effects while still controlling their cancer effectively.

Participant Groups

Group I: Experimental Arm: Cycle 5+ Partial Response or Better Experimental Treatment 2 Interventions

Subjects will be treated the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams/kilograms daily days 1-21 out of a 28 day cycle

Group II: Experimental Arm: Cycle 1-4 All subjects Active Control 3 Interventions

Subjects will be treated with the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle * Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab

Group III: Experimental Arm: Cycle 5+ Less than Partial Response Active Control 3 Interventions

Subjects will be treated the following: * Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks * Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle * Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Findings from Research

In the POLLUX study, after 25.4 months of follow-up, the combination of daratumumab with lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma, with a hazard ratio of 0.41 compared to lenalidomide/dexamethasone alone.

The overall response rate was notably higher with the daratumumab combination (92.9%) compared to the control (76.4%), and a significant proportion of patients achieved minimal residual disease negativity (26.2% vs 6.4%), indicating a deeper response without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Dimopoulos, MA., San-Miguel, J., Belch, A., et al.[2019]

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]

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, 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]

A review of 94 safety reports on erenumab, galcanezumab, and fremanezumab found no significant increase in spontaneous abortion or major birth defects, suggesting these medications may be relatively safe during pregnancy and lactation.

Despite the lack of strong evidence for maternal toxicities or adverse outcomes, the limited number of reports and absence of long-term safety data indicate that ongoing monitoring of these drugs in pregnant and lactating women is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database. Noseda, R., Bedussi, F., Gobbi, C., et al.[2021]

In a study involving 401 rheumatoid arthritis patients over a mean follow-up of 70 weeks, rituximab treatment led to a significant reduction in disease activity, as measured by the DAS28-ESR score, from 6.0 at baseline to 4.2 at week 16.

Retreatment with rituximab was more effective when administered before patients showed significant disease flare, indicating that earlier intervention could optimize treatment outcomes for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization of rituximab treatment strategies. Vander Cruyssen, B., Durez, P., Westhovens, R., et al.[2022]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

Combining lenalidomide with daratumumab significantly enhances the ability of the immune system to kill multiple myeloma cells, as shown in assays using both cell lines and primary patient cells.

The synergy between lenalidomide and daratumumab was particularly evident in the bone marrow environment of multiple myeloma patients, suggesting that this combination could be a powerful treatment strategy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. van der Veer, MS., de Weers, M., van Kessel, B., et al.[2021]

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]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. [2019]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

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

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

Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial. [2022]

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

Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization of rituximab treatment strategies. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Risk of Malignancies in Patients with Rheumatoid Arthritis Treated with Rituximab: Analyses of Global Postmarketing Safety Data and Long-Term Clinical Trial Data. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. [2022]

11. Italy pubmed.ncbi.nlm.nih.gov

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. [2021]

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

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

13. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]