Drug Combination for Relapsed Multiple Myeloma

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Anticoagulants

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Compensation: Varies

Number of Visits: 1

Duration: 9+ months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to help people with relapsed multiple myeloma, a type of blood cancer that returns after treatment. The study involves four medications: elotuzumab (Empliciti), pomalidomide (Pomalyst or Imnovid), bortezomib (Velcade), and dexamethasone (Decadron or Dexone). Participants will receive these medications through an IV or by taking pills, following a set schedule. Those who have tried at least one prior treatment and experienced a return of their multiple myeloma might be suitable for this trial. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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 participate if you have had chemotherapy or radiotherapy within 2 weeks before the study, or if you are on high-dose corticosteroids, except for certain conditions. It's best to discuss your specific medications with the study team.

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

Research has shown that the combination of elotuzumab, pomalidomide, bortezomib, and dexamethasone is generally manageable for patients. Studies have found that people with relapsed multiple myeloma who used this combination experienced manageable side effects. Despite most patients having tried several treatments before this one, the side effects remained acceptable.

While all medications can cause side effects, this combination's safety appears promising. Patients commonly reported tiredness and low blood cell counts, but these were not severe for most. This combination has been used in other studies and has proven effective while maintaining a reasonable level of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for relapsed multiple myeloma because it brings together four powerful drugs: bortezomib, dexamethasone, elotuzumab, and pomalidomide. Unlike standard treatments, this combo includes elotuzumab, a monoclonal antibody that specifically targets the SLAMF7 protein on myeloma cells, boosting the immune system's ability to fight the cancer. The varied delivery methods—oral, intravenous, and subcutaneous—ensure that each drug is administered in the most effective way for maximum impact. This approach offers a fresh hope for tackling multiple myeloma that has returned after initial treatment.

What evidence suggests that this trial's treatments could be effective for relapsed Multiple Myeloma?

Research has shown that a combination of four drugs—elotuzumab, pomalidomide, bortezomib, and dexamethasone—may help treat relapsed and refractory multiple myeloma. In this trial, participants will receive this combination treatment. Studies have found that pomalidomide, bortezomib, and dexamethasone work well together. Elotuzumab, a protein that boosts the immune system, has proven effective in similar drug combinations for treating multiple myeloma. These drugs target cancer cells in different ways, potentially leading to better disease control. Overall, this combination aims to improve treatment for patients who have not responded well to previous therapies. ^{1 5 6 7 8}

Who Is on the Research Team?

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed Multiple Myeloma who have had at least one prior therapy including lenalidomide and a proteasome inhibitor. Participants must have measurable disease indicators, such as specific levels of monoclonal protein in blood or urine, and be physically able to perform daily activities (ECOG ≤ 2).

Inclusion Criteria

My white blood cell count is healthy and I haven't used G-CSF recently.

I have had treatment for my multiple myeloma that came back or didn't respond to treatment.

I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

Participants who are receiving any other investigational agents

I am not on high dose corticosteroids, except for certain conditions.

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elotuzumab, pomalidomide, bortezomib, and dexamethasone in 28-day cycles

9+ months

Weekly visits for cycles 1-2, bi-weekly for cycles 3-8, monthly for cycles 9+

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Dexamethasone
• Elotuzumab
• Pomalidomide

Trial Overview The study tests a combination treatment for Multiple Myeloma using Elotuzumab, Pomalidomide, Bortezomib, and Dexamethasone. It aims to find out how effective this drug mix is for those whose cancer has returned after previous treatments.

How Is the Trial Designed?

Group I: Elotuzumab, pomalidomide, bortezomib, dex Experimental Treatment 4 Interventions

Each cycle is 28 days. Elotuzumab will be administered by intravenous infusion. For cycles 1-2, elotuzumab will ge given weekly. For cycles 3-8, elotuzumab will be given every other week. For cycles 9+, elotuzumab will be given on day 1. Pomalidomide will be given orally on days 1-21. Bortezomib will be given weekly subcutaneously on days 1, 8, 15. Dexamethasone will be given as a combination orally and intravenously.

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Published Research Related to This Trial

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Thalidomide, when used as a first-line treatment combined with conventional chemotherapy, has been shown to improve survival rates in patients over 65, despite its potential toxicity to the peripheral nervous system.

Bortezomib and lenalidomide, both effective in treating myeloma relapse, can be used in combination with dexamethasone and each other, indicating a shift towards using these agents to manage myeloma as a chronic disease rather than relying solely on traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. Moreau, P.[2019]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

Pomalidomide is a new immunomodulatory drug (IMiD) that has shown more potent anti-myeloma activity compared to existing IMiDs like thalidomide and lenalidomide, with a similar safety profile.

In clinical trials, pomalidomide combined with low-dose dexamethasone has demonstrated effectiveness in myeloma patients who are resistant to other treatments, leading to its accelerated approval by the FDA and EMA as a new strategy for relapsed and refractory myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data. Offidani, M., Corvatta, L., Caraffa, P., et al.[2014]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39626297/

Elotuzumab in combination with pomalidomide, bortezomib ... The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/5/1163/534297/Elotuzumab-in-combination-with-pomalidomide

Elotuzumab in combination with pomalidomide, bortezomib ... There has been a dramatic improvement in outcomes in multiple myeloma in recent years from using immunomodulatory drugs, proteasome inhibitors, ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1805762

Elotuzumab plus Pomalidomide and Dexamethasone for ... The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory ...

4. nature.com nature.com/articles/s41408-025-01310-z

Real world outcomes with elotuzumab-based therapies for ... In this retrospective analysis, we aim to evaluate the real-world efficacy and the clinical outcomes of RRMM patients treated with Elo+ImiD+Dex regimens.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9870233/

Elotuzumab Plus Pomalidomide and Dexamethasone for ... Despite substantial improvements in multiple myeloma (MM) therapies in the past 10-15 years, the 5-year relative survival rate is 55.6%. MM is mostly incurable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11925518/

Elotuzumab in combination with pomalidomide, bortezomib ... Elotuzumab combined with PVd is a novel, 4 drug combination in relapsed MM. The regimen is tolerated well and effective in patients with a median of 3 prior ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02718833

A Study of Elotuzumab With Pomalidomide, Bortezomib ... This research study is a phase II clinical trial, the investigators are studying the safety and response rate of the combinations of elotuzumab, ...

8. onclive.com onclive.com/view/elotuzumab-plus-pvd-has-antitumor-activity-in-heavily-pretreated-r-r-myeloma

Elotuzumab Plus PVd Has Antitumor Activity in Heavily ... Elotuzumab plus PVd elicited responses in patients with relapsed/refractory multiple myeloma after a median of 3 prior lines of therapy.