Pomalidomide with Stem Cell Transplant for Multiple Myeloma

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Lenalidomide

Must not be taking: Thalidomide, Pomalidomide

Disqualifiers: HIV, Hepatitis B/C, Uncontrolled illness, 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: 4

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well pomalidomide (also known as Pomalyst) can reduce myeloma cells in bones by comparing two treatment methods for people with multiple myeloma. Participants will first receive a combination of clarithromycin, pomalidomide, and dexamethasone (a type of steroid) for four cycles. Afterward, one group will undergo a stem cell transplant (also known as hematopoietic stem cell transplantation) followed by pomalidomide, while the other group will continue with the drug combination and pomalidomide maintenance. The trial aims to determine which approach is more effective. It is suitable for individuals with relapsed multiple myeloma who have previously undergone a stem cell transplant with a remission lasting at least a year. 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 does not specify if you need to stop taking your current medications. However, you cannot have had myeloma therapy within 14 days before starting the study, and you cannot be on other investigational drugs.

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

Research has shown that the combination of clarithromycin, pomalidomide, and dexamethasone, known as ClaPD, is generally manageable for patients. In one study, about 60% of patients responded well to ClaPD, with nearly 25% experiencing a very good partial improvement. This suggests that the treatment can be effective for multiple myeloma without causing severe side effects.

Another study found this combination manageable for patients with relapsed myeloma, as it did not cause many serious issues. Patients continued the treatment for over seven months on average, indicating that side effects were not too difficult to manage.

Overall, while every treatment can have side effects, these studies suggest that the ClaPD combination, whether followed by a stem cell transplant or used on its own, is fairly well-tolerated by patients. ^{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 combine medications with a stem cell transplant, potentially offering a new way to tackle the disease. Unlike standard treatments like lenalidomide or bortezomib, this approach uses pomalidomide, which may work better for patients who haven't responded well to other drugs. Additionally, the combination with clarithromycin and dexamethasone might enhance the effectiveness of pomalidomide. For those who undergo the stem cell transplant, the procedure could provide a more robust and lasting response by using high-dose chemotherapy followed by healthy stem cell infusion.

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

Studies have shown that a combination of clarithromycin, pomalidomide, and dexamethasone can effectively treat multiple myeloma, a type of blood cancer. This treatment achieves a 60% success rate, with 23% of patients experiencing a very good partial response, indicating a significant reduction in cancer symptoms. Research suggests that adding clarithromycin enhances the effectiveness of pomalidomide and dexamethasone. In this trial, some participants will receive this combination alone, while others will receive it followed by a stem cell transplant. For those who also undergo a stem cell transplant, this approach may further improve results. Overall, these findings suggest that this combination could be a promising option for reducing cancer cells in the bone. ^{1 2 3 6 7}

Who Is on the Research Team?

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed multiple myeloma who've had a stem cell transplant and remission lasting at least 12 months. They must have measurable disease, good organ/marrow function, be able to take blood thinners, understand the study consent, and comply with POMALYST REMS™ program requirements.

Inclusion Criteria

My multiple myeloma has returned after treatment, as confirmed by tests.

A doctor has approved me for a stem cell transplant.

I can take care of myself and perform normal activities without assistance.

Exclusion Criteria

I haven't had myeloma treatment in the last 14 days and have recovered from any past treatment side effects.

I do not have any uncontrolled illnesses that would affect my participation.

Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

All patients receive 4 cycles of clarithromycin, pomalidomide, and dexamethasone (ClaPD)

16 weeks

4 visits (in-person)

Group 1: Stem Cell Transplant

Patients undergo autologous stem cell transplant followed by pomalidomide maintenance

4 weeks for transplant, followed by maintenance

Group 2: Continued ClaPD

Patients continue to receive ClaPD for 9 cycles followed by pomalidomide maintenance

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• Clarithromycin
• Dexamethasone
• Pomalidomide
• Stem Cell Transplant

Trial Overview The trial compares two treatments using pomalidomide: one group gets an autologous stem cell transplant followed by maintenance pomalidomide; the other continues on clarithromycin/pomalidomide/dexamethasone (ClaPD) therapy before switching to pomalidomide maintenance.

How Is the Trial Designed?

Group I: Clarithromycin + Pomalidomide + Dexamethasone Alone Experimental Treatment 3 Interventions

All patients will receive 4 cycles of clarithromycin 500mg twice daily on days 1-28 pomalidomide 4 mg daily on days 1 through 21 and dexamethasone orally at a dose of 40 mg daily on days 1, 8, 15, and 22 of each 28 day cycle. Patients assigned to ClaPD alone will receive 5 additional cycles of ClaPD.

Group II: Clarithromycin + Pomalidomide + Dexamethasone + stem cell Experimental Treatment 3 Interventions

All patients will receive 4 cycles of clarithromycin 500mg twice daily on days 1-28, pomalidomide 4 mg daily on days 1 through 21 and dexamethasone orally at a dose of 40 mg daily on days 1, 8, 15, and 22 of each 28-day cycle. Patients randomized to auto-SCT will proceed within 28 days after completion of the 4th cycle of ClaPD to receive melphalan 140mg/m2 or 200mg/m2 (as per institutional guidelines) followed by hematopoietic cell infusion.

Clarithromycin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in European Union as Klaricid for:

• Acute bacterial exacerbation of chronic bronchitis
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in Canada as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Rutgers Cancer Institute of New Jersey

Collaborator

Trials

72

Recruited

22,200+

North Shore University Hospital

Collaborator

Trials

15

Recruited

3,700+

State University of New York - Upstate Medical University

Collaborator

Trials

176

Recruited

27,600+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Published Research Related to This Trial

The BLT-D regimen, which combines clarithromycin, low-dose thalidomide, and dexamethasone, showed a high response rate of 93% in 50 patients with multiple myeloma, indicating its efficacy as a treatment option.

While the treatment was generally well-tolerated, neurotoxicity was the main reason for discontinuation, and caution is advised for patients with existing health issues like severe cardiopulmonary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. Coleman, M., Leonard, J., Lyons, L., 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]

Pomalidomide, in combination with dexamethasone, significantly improves progression-free survival in adult patients with relapsed and refractory multiple myeloma, with a median of 15.7 weeks compared to 8.0 weeks for high-dose dexamethasone alone, based on a phase III study with previously treated patients.

Common side effects of pomalidomide include anemia, neutropenia, and thrombocytopenia, with a notable risk of teratogenic effects, highlighting the need for careful monitoring and management of adverse reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use. Hanaizi, Z., Flores, B., Hemmings, R., et al.[2018]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30792190/

Phase 2 study of clarithromycin, pomalidomide, and ... - PubMed The overall response rate (ORR) was 60% with 23% achieving at least a very good partial response. There was no statistical difference in ...

2. ashpublications.org ashpublications.org/bloodadvances/article/3/4/603/246748/Phase-2-study-of-clarithromycin-pomalidomide-and

Phase 2 study of clarithromycin, pomalidomide, and ... The overall response rate (ORR) was 60% with 23% achieving at least a very good partial response. There was no statistical difference in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6391672/

Phase 2 study of clarithromycin, pomalidomide, and ... The overall response rate (ORR) achieved was 30% with a median duration of response of 7 months. The results with the Pom-dex doublet prompted ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.15_suppl.8036

Clarithromycin, pomalidomide, and dexamethasone ... Responses were progressive disease: 10%, stable disease: 21%, minimal response: 12%, partial response: 33%, very good partial response: 18%, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000020

Clarithromycin, ixazomib, pomalidomide, dexamethasone ... The ORR was 75% with a DCR of 100%, paired with a median PFS of almost 2 years, indicating good clinical efficacy and tolerability in this cohort of patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02542657

Study Details | NCT02542657 | Ixazomib with ... This phase I/II trial studies the side effects and best dose of clarithromycin when given together with ixazomib citrate, pomalidomide, and dexamethasone ...

7. multiplemyelomahub.com multiplemyelomahub.com/medical-information/clarithromycin-pomalidomide-and-dexamethasone-in-patients-with-relapsed-or-refractory-multiple-myeloma-results-from-a-phase-ii-study

Clarithromycin, pomalidomide and dexamethasone in ... Median follow-up: 20.3 months (0.3–92.7) · Median time on study: 7.2 months (0.3–57.2) · ORR: 60% (n = 70) · Very good partial response (VGPR): 23% ...