Pomalidomide + Dexamethasone +/- Daratumumab for Multiple Myeloma

(POM MM 014 Trial)

Recruiting at 95 trial locations

Overseen By Associate Director Clinical Trial Disclosure, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Must not be taking: Pomalidomide, Daratumumab

Disqualifiers: Severe renal impairment, Heart failure, HIV, 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: 1

Duration: Up to 7 years

186 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will evaluate the efficacy and safety of combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex) (Cohort A) or the combination of pomalidomide (POM) , daratumumab (DARA) and low-dose dexamethasone (LD-Dex) (Cohort B) in subjects with relapsed or refractory multiple myeloma who have received a first or second line treatment of lenalidomide-based therapy. This trial will test the hypothesis for Cohort A that the proportion of patients will have an Overall Response Rate (ORR) of \> 30 % to reveal that Pomalidomide is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort B that the proportion of patients will have an Overall Response Rate (ORR) of \> 70 % to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort C that the proportion of patients will have an Overall Response Rate (ORR) of \>60% to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This treatment will be in only Japanese patients.

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 cannot have used any anti-myeloma drug therapy within 14 days before starting the trial treatment.

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

Research shows that adding Daratumumab to Pomalidomide and Dexamethasone improves the response rate and survival in patients with multiple myeloma who have already tried other treatments. In one study, 60% of patients responded to this combination, and it was generally well-tolerated, although it did increase the risk of low white blood cell counts. ^{1 2 3 4 5}

Is the combination of Pomalidomide, Dexamethasone, and Daratumumab safe for humans?

The combination of Pomalidomide, Dexamethasone, and Daratumumab has been studied in patients with multiple myeloma and is generally considered safe, though it can cause side effects like neutropenia (low white blood cell count), anemia (low red blood cell count), and infusion-related reactions. These side effects are similar to those seen with the individual drugs, with the exception of more frequent neutropenia when Daratumumab is added. ^{1 2 3 4 6}

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

This drug combination is unique because it adds Daratumumab, a monoclonal antibody that targets a specific protein on myeloma cells, to the existing treatment of Pomalidomide and Dexamethasone, which enhances the immune response and improves progression-free survival in patients who have already undergone multiple treatments. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with relapsed or refractory multiple myeloma who have previously been treated with lenalidomide. Participants must have measurable disease, acceptable organ and marrow function, and an ECOG score of 0-2. Women must avoid pregnancy and breastfeeding; men must use contraception. Exclusions include severe renal impairment, recent other treatments, certain infections like HIV/hepatitis, heart conditions, allergies to study drugs or their components.

Inclusion Criteria

All subjects must agree not to share medication

I agree to use a condom during sexual activity while in the study and for some time after.

I agree not to donate semen during and up to 3 months after treatment.

Exclusion Criteria

Your platelet count is too low, depending on the percentage of a certain type of cells in your bone marrow.

You are allergic to mannitol, corticosteroids, monoclonal antibodies, human proteins, or mammalian-derived products.

I have severe heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pomalidomide and low-dose dexamethasone, with or without daratumumab, in 28-day cycles

Up to 7 years

Cycle 1-2: Weekly visits; Cycle 3-6: Bi-weekly visits; Cycle 7+: Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years

Treatment Details

Interventions

• Daratumumab
• Dexamethasone
• Pomalidomide

Trial Overview The trial tests the effectiveness of pomalidomide with low-dose dexamethasone (Cohort A), or this combination plus daratumumab (Cohorts B & C). Cohort A aims for a >30% response rate in patients previously treated with lenalidomide. Cohorts B & C target >70% and >60% response rates respectively; Cohort C includes only Japanese patients.

Participant Groups

Group I: Pomalidomide + dexamethasone Experimental Treatment 2 Interventions

Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.

Group II: Pomalidomide + Dexamethasone + Daratumumab Experimental Treatment 3 Interventions

Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/ day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle and daratumumab administered intravenously (IV) at a starting dose of 16 mg/kg at following schedule: * Days 1, 8, 15, and 22 of a 28-day cycle for Cycle 1 and Cycle 2 * Days 1 and 15 for Cycle 3 through Cycle 6 * Day 1 for Cycle 7 and each cycle thereafter until disease progression

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?

Celgene

Lead 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

Findings from Research

In a phase 3 trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab with pomalidomide and dexamethasone significantly improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median of 12.4 months versus 6.9 months.

While the combination treatment was effective, it was associated with a higher incidence of grade 3 or 4 adverse events, particularly neutropenia, indicating that while daratumumab enhances treatment efficacy, it may also increase the risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2021]

Daratumumab significantly improves overall survival (OS) compared to pomalidomide plus low-dose dexamethasone in patients with heavily pretreated multiple myeloma, with hazard ratios indicating a strong treatment benefit (0.56 and 0.51 for two different studies).

The survival advantage of daratumumab is even more pronounced in patients who have not previously been treated with pomalidomide, suggesting it may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. Van Sanden, S., Ito, T., Diels, J., et al.[2019]

The combination of daratumumab, pomalidomide, and low-dose dexamethasone is shown to be a safe and effective treatment for relapsed/refractory multiple myeloma, with significant immune system enhancements observed in patients.

Treatment led to increased activation and proliferation of T cells, particularly CD8+ T cells, while also reducing certain immune cell types, suggesting a mechanism for improved immune-mediated tumor destruction without increasing exhausted T-cell phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. Pierceall, WE., Amatangelo, MD., Bahlis, NJ., et al.[2021]

In a study of 103 patients with relapsed/refractory multiple myeloma, the combination of daratumumab, pomalidomide, and dexamethasone showed an overall response rate of 60%, indicating significant efficacy even in patients with a history of multiple prior therapies.

The safety profile of this combination treatment was similar to pomalidomide and dexamethasone alone, with the main exception being a higher incidence of neutropenia and infusion-related reactions, but without an increase in infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Chari, A., Suvannasankha, A., Fay, JW., et al.[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]

References

1. England pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. [2019]

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

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. [2021]

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

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Daratumumab and its use in the treatment of relapsed and/or refractory multiple myeloma. [2020]