Daratumumab vs Lenalidomide for Multiple Myeloma

Not currently recruiting at 9 trial locations

Overseen By Sham Mailankody, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Anticoagulants, Antivirals

Must not be taking: Investigational agents

Disqualifiers: Progressive myeloma, COPD, Asthma, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 cycles (each cycle is 28 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which maintenance therapy, daratumumab (Darzalex) or lenalidomide (Revlimid), provides a better quality of life for individuals with multiple myeloma, a type of blood cancer, who have responded well to initial treatment. Participants will receive either daratumumab or lenalidomide, and researchers will assess their quality of life through various questionnaires. The trial suits individuals whose multiple myeloma remains stable after initial therapy and who can take preventive medications for blood clots and viral infections. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to take daily preventive medications for blood clots and viral infections, like aspirin and acyclovir.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that daratumumab, when used alone, caused infections in some patients. About 77.5% experienced infections, most commonly upper respiratory tract infections, such as colds or sinus issues. However, daratumumab has demonstrated strong results in treating multiple myeloma, helping patients live longer without disease progression.

Research on lenalidomide shows it can extend patient survival when combined with dexamethasone. A common side effect is decreased appetite, affecting about 23% of patients. Only a small number, around 3%, experienced weight loss or malnutrition.

Both treatments have shown benefits in studies, though they come with some side effects. If considering joining this trial, these are potential side effects. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they offer new approaches compared to traditional options like bortezomib and thalidomide. Daratumumab is unique as it targets a specific protein on cancer cells, helping the immune system attack the cancer more effectively. Unlike most standard treatments that are administered orally or intravenously, daratumumab is given as a subcutaneous injection, potentially making it more convenient for patients. Lenalidomide, on the other hand, continues to be a crucial component in multiple myeloma treatment by modulating the immune system and inhibiting cancer cell growth, but its maintenance therapy in this trial may optimize long-term management. Additionally, both treatments are paired with a sub-study on a whole food plant-based diet, which might enhance patient outcomes by focusing on overall health and well-being.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will compare daratumumab and lenalidomide for maintenance therapy in multiple myeloma. Research has shown that daratumumab, which participants in this trial may receive, is very effective in treating multiple myeloma. In one study, 95% of patients who had no detectable cancer cells for a long time did not see their disease worsen for four years. Another study found that daratumumab given as an injection under the skin worked just as well as when given through an IV. Lenalidomide, another treatment option in this trial, has shown mixed results. One study showed that 55% of patients responded to it, with the disease not worsening for about 10 months on average. However, lenalidomide did help patients live longer compared to some other treatments in past studies. Both treatments have shown benefits, but recent research suggests daratumumab may be more promising. ^{1 2 6 7 8}

Who Is on the Research Team?

Urvi Shah, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with newly diagnosed multiple myeloma who've responded well to initial treatment. They must be able to take antiviral and anticoagulation meds, understand the consent form, and women of childbearing age must avoid pregnancy and adhere to REMS program requirements. Participants should have proper kidney, liver function, and agree to birth control measures.

Inclusion Criteria

Your platelet count is at least 50,000 per microliter.

I had a stem cell transplant over 100 days ago.

I agree not to donate eggs/sperm for 3 months after stopping daratumumab.

Exclusion Criteria

I am not participating in the nutrition sub-study.

I do not have any uncontrolled illnesses or social situations that would affect my study participation.

My condition did not improve or worsened while on lenalidomide or daratumumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either daratumumab or lenalidomide as maintenance therapy. Daratumumab is administered as a subcutaneous injection, and lenalidomide is taken orally.

36 cycles (each cycle is 28 days)

Multiple visits per cycle as per drug administration schedule

Sub-study (optional)

Participants may opt into a sub-study involving a whole food plant-based diet and nutrition counseling for 12 weeks.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with quality of life questionnaires collected at therapy discontinuation and 1-month post therapy.

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Lenalidomide

Trial Overview The study compares usual maintenance therapy (lenalidomide) with daratumumab as a new option for maintaining health in multiple myeloma patients post-treatment. Quality of life will be assessed through questionnaires to determine if daratumumab offers better outcomes than lenalidomide.

How Is the Trial Designed?

Group I: Lenalidomide maintenance Experimental Treatment 3 Interventions

Arm A: Those randomized to lenalidomide maintenance will receive a maintenance dose of 10mg oral lenalidomide on days 1-21 of each 28-day cycle. HRQoL with EORTC QLQ-C30, EORTC QLQ-MY20 and PRO-CTCAE questionnaires will be collected: prior to therapy initiation (baseline); day 1 of cycle 2 and every cycle day 1 thereafter; at therapy discontinuation, and at 1-month post therapy follow-up. Sub ARM A: The first 15 patients on each arm interested in this sub study will be enrolled during C10D1 visit to initiate whole food plant based diet (WFPBD) meals provided by Daily Harvest and nutrition counseling for 12 weeks. They will continue on their lenalidomide maintenance schedule per study calendar. The patients who do not go on the nutrition sub study will continue on their lenalidomide maintenance schedule per study calendar.

Group II: Daratumumab maintenance Experimental Treatment 3 Interventions

ARM B: Those randomized to receive daratumumab maintenance will receive 1800 milligrams (mg) subcutaneous (SC) injection of daratumumab as follows: days 1, 8, 15, and 22 of cycles 1 and 2; days 1 and 15 of cycles 3-6; day 1 of cycles 7-36. HRQoL with EORTC QLQ-C30, EORTC QLQ-MY20 and PRO-CTCAE questionnaires will be collected: prior to therapy initiation (baseline); day 1 of cycle 2 and every cycle day 1 thereafter; at therapy discontinuation, and at 1-month post therapy follow-up. Sub ARM B: The first 15 patients on each arm interested in this sub study will be enrolled during C10D1 visit to initiate whole food plant based diet (WFPBD) meals provided by Daily Harvest and nutrition counseling for 12 weeks. They will continue on their daratumumab maintenance schedule per study calendar. The patients who do not go on the nutrition sub study will continue on their daratumumab maintenance schedule per study calendar.

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Daratumumab combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

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 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]

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 received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a real-world study of 240 relapsed/refractory multiple myeloma patients, treatment with daratumumab, lenalidomide, and dexamethasone (Dara-Rd) resulted in a significantly higher overall response rate (91.2%) compared to lenalidomide and dexamethasone (Rd) alone (69.9%).

Patients receiving Dara-Rd experienced a median progression-free survival (PFS) of 26.9 months, compared to 12.8 months for those on Rd, indicating that Dara-Rd is more effective, especially in patients with fewer prior treatments. However, in patients with more than three previous treatment lines, the benefits of Dara-Rd were not significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma patients - real world evidence analysis. Stork, M., Spicka, I., Radocha, J., et al.[2023]

Daratumumab, a monoclonal antibody targeting CD38, shows significantly improved overall survival in patients with multiple myeloma who have undergone extensive prior treatments, with an adjusted overall survival-hazard ratio of 0.33 based on a study of 148 patients compared to historical controls.

The study highlights that daratumumab is particularly effective in heavily pretreated patients, including those who are triple or quadruple refractory to other therapies, indicating its potential as a critical treatment option in advanced multiple myeloma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. Usmani, SZ., Diels, J., Ito, T., et al.[2021]

Citations

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DARZALEX FASPRO® (daratumumab and hyaluronidase ... DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen shows 95 percent progression-free survival at four years in transplant- ...

2. darzalex.com darzalex.com/clinical-results/

Clinical Results A study confirmed that DARZALEX FASPRO ® gave patients results comparable to the IV formulation of DARZALEX ® in treating multiple myeloma when used by itself.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141371/

Real-world data on the use of subcutaneous daratumumab ... As of the data cutoff (August 8, 2023), 49 patients were included. By the end of consolidation, 91.7% of patients achieved an overall response ( ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/multiple-myeloma-darzalex-plus-vrd

Daratumumab Plus Standard Therapy for Multiple Myeloma Slightly more patients in the daratumumab group than the standard treatment group were able to receive a stem cell transplant (90% versus 87%).

5. jnj.com jnj.com/media-center/press-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care

TECVAYLI® plus DARZALEX FASPRO® combination ... In transplant-eligible patients with newly diagnosed multiple myeloma, a 100 percent overall response rate was achieved when given as the first ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-darzalex-faspro-adverse-event-infections-in-patients-with-newly-diagnosed-multiple-myelo

DARZALEX + DARZALEX FASPRO - Adverse Event Results - Safety - Infection-Related Events in Part 2 · Infections occurred in 77.5% (n=341) of patients in the DARZALEX monotherapy arm vs 64% ( ...

7. darzalexhcp.com darzalexhcp.com/frontline-dvrd/

Frontline DVRd In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse ...

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DARZALEX FASPRO® (daratumumab and hyaluronidase ... Overall survival was also extended with DARZALEX FASPRO®, with 5-year survival rates of 93 percent versus 86.9 percent for active monitoring (HR ...