Pomalidomide + Dexamethasone +/- Daratumumab for Multiple Myeloma

(POM MM 014 Trial)

No longer recruiting at 100 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for people with multiple myeloma, a type of blood cancer, who did not respond well to previous therapies. It tests two combinations: one with pomalidomide, an immunomodulatory drug, and dexamethasone, a corticosteroid; the other adds daratumumab, an antibody therapy, to the mix. The goal is to evaluate the effectiveness and safety of these combinations. Ideal candidates have already tried a lenalidomide-based treatment and experienced a return or worsening of their disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that the combination of pomalidomide and low-dose dexamethasone is generally safe for patients with relapsed or refractory multiple myeloma. One study found it effective and well-tolerated by Chinese patients with this condition. Another study added daratumumab to this combination and found that 54% of patients experienced serious side effects, though the treatment remained effective.

Overall, these treatments have demonstrated promising results in terms of safety and effectiveness. However, some patients experienced serious side effects, particularly when daratumumab was included. Prospective participants should discuss any concerns or questions with the trial team before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple myeloma, which often include medications like lenalidomide or bortezomib, the combination of pomalidomide and dexamethasone, with or without daratumumab, is gaining attention. Researchers are excited because daratumumab specifically targets a protein called CD38 on myeloma cells, helping the immune system recognize and destroy these cancerous cells more effectively. Additionally, adding daratumumab to the mix could enhance the overall effectiveness of the treatment, potentially leading to better outcomes for patients. This approach represents a promising advancement in targeting multiple myeloma cells more precisely and efficiently.

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

Research has shown that using pomalidomide and dexamethasone together can help treat multiple myeloma that has returned or hasn't responded to other treatments. Approximately 35.8% of patients experience some improvement with this combination. In this trial, one group of participants will receive pomalidomide and dexamethasone, while another group will receive these drugs along with daratumumab. Studies indicate that adding daratumumab to these drugs enhances the treatment's effectiveness, with up to 94% of patients responding to this combination and many experiencing a complete recovery. These results highlight the potential of these treatments for managing multiple myeloma, especially for those who haven't had success with other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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

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

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

I have severe heart failure.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660104/

The real‐world use and efficacy of pomalidomide for ... Real‐world evidence of efficacy and safety of pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: Czech registry data.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023002288

A Meta-Analysis of the Efficacy of Pomalidomide-Based ... Pomalidomide-based combination regimens were effective in patients with RRMM previously treated with lenalidomide and tended to be associated with better ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3291492/

Pomalidomide plus low-dose dexamethasone in myeloma ... Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using ...

4. nature.com nature.com/articles/s41408-025-01356-z

an Asian Myeloma Network study (AMN003) Pomalidomide has been shown to improve survival in patients with relapsed/refractory myeloma (RRMM). However, the optimal pomalidomide-based ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/jha2.774

The real‐world use and efficacy of pomalidomide for ... Patients treated with Pd in this cohort had a partial response or better (≥ PR) rate of 35.8% and median time to next treatment (mTNT) of 4.9 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35778685/

a multicenter, prospective, single-arm, phase 2 trial Conclusions: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. Trial registration: The ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024002854

Pomalidomide/Daratumumab/Dexamethasone in ... At a median follow-up of 13.1 months, overall response rate (ORR) was 60.2%, median progression-free survival (PFS) was 8.8 months, and median overall survival ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02119468

Ixazomib Plus Pomalidomide and Dexamethasone in ... Giving ixazomib with pomalidomide and dexamethasone may be an effective treatment for relapsed or relapsed/refractory multiple myeloma.

9. myeloma.org myeloma.org/pomalyst-pomalidomide

Pomalyst (Pomalidomide) for Multiple Myeloma | The IMF Data showed comparable efficacy and safety with both Sarclisa IV and Sarclisa OBI, supporting potential use of an OBI to improve patient experience. Patient ...

10. ashpublications.org ashpublications.org/bloodadvances/article/7/24/7581/498616/Pomalidomide-bortezomib-and-dexamethasone-for

Pomalidomide, bortezomib, and dexamethasone for newly ... The pomalidomide-bortezomib-dexamethasone (PVD) combination has been approved in relapsed/refractory MM (R/R MM) based on the results of phase 3 ...