Drug Combination for Relapsed Multiple Myeloma

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

52 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination for relapsed multiple myeloma?

Research shows that pomalidomide, when combined with low-dose dexamethasone, is effective for patients with relapsed multiple myeloma, especially those who have not responded to other treatments like lenalidomide and bortezomib. This combination has been shown to improve survival rates and response rates in clinical trials. ^{1 2 3 4 5}

Is the drug combination of pomalidomide and dexamethasone safe for humans?

The combination of pomalidomide and low-dose dexamethasone has been shown to have a manageable safety profile in patients with relapsed and refractory multiple myeloma, with common side effects including low white blood cell counts, infections, anemia (low red blood cell count), and low platelet counts. ^{1 2 6 7 8}

What makes the drug combination of Bortezomib, Dexamethasone, Elotuzumab, and Pomalidomide unique for treating relapsed multiple myeloma?

This drug combination is unique because it combines multiple mechanisms of action, including immunomodulatory effects, proteasome inhibition, and direct myeloma cell death, to target relapsed multiple myeloma, especially in patients who have already tried other treatments like lenalidomide and bortezomib. This approach aims to improve patient outcomes by using a synergistic effect of these drugs. ^{1 2 4 7 9}

What is the purpose of this trial?

This research study is studying a combination of study drugs as a possible treatment for relapsed and refractory Multiple Myeloma. The interventions involved in this study are elotuzumab, pomalidomide, bortezomib, dexamethasone.

Research Team

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

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

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

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

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

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Pomalidomide in the management of relapsed multiple myeloma. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data. [2014]

6. Italy pubmed.ncbi.nlm.nih.gov

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma. [2018]

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

Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. [2022]

8. Germany 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. [2021]

9. France pubmed.ncbi.nlm.nih.gov

[New drugs for myeloma]. [2019]