Pomalidomide with Stem Cell Transplant for Multiple Myeloma

Recruiting in Syracuse (>99 mi)

+10 other 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see whether pomalidomide (also known as Pomalyst) reduces the number of myeloma cells in the bones, and to see what is the best way to use pomalidomide in patients with myeloma. To do this, the investigators want to compare two types of treatment using pomalidomde. This is a randomized trial which means that the decision as to which treatment the patient will receive will be made by a computer, much like flipping a coin. All patients start by receiving 4 cycles of clarithromycin, pomalidomide and dexamethasone (ClaPD). After 4 cycles, half of the patients will undergo an autologous stem cell transplant followed by pomalidomide (Group 1). The other half of the patients will continue to receive ClaPD for 9 cycles to be followed by pomalidomide maintenance. (Group 2). At the end of the study, the two groups will be compared to see if there is a difference in disease outcome.

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.

What data supports the effectiveness of the drug Pomalidomide with Stem Cell Transplant for Multiple Myeloma?

Research shows that Pomalidomide, when combined with low-dose dexamethasone, is effective in treating relapsed and refractory multiple myeloma, leading to longer survival and better response rates. Additionally, similar regimens involving clarithromycin, thalidomide, and dexamethasone have shown high response rates in multiple myeloma patients. ^{1 2 3 4 5}

Is the combination of pomalidomide, clarithromycin, and dexamethasone safe for treating multiple myeloma?

The combination of pomalidomide, clarithromycin, and dexamethasone has been studied for safety in treating multiple myeloma. Common side effects include low levels of white blood cells (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia). These side effects are generally manageable, and the treatment is considered to have a tolerable safety profile. ^{1 2 3 6 7}

What makes the treatment with Pomalidomide, Dexamethasone, and Stem Cell Transplant unique for multiple myeloma?

This treatment is unique because it combines pomalidomide, an oral drug that modifies the immune system, with dexamethasone and a stem cell transplant, offering a novel approach for patients with relapsed or hard-to-treat multiple myeloma who have limited options after other treatments have failed. ^{1 4 5 8 9}

Research Team

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Patients who participate in this study must be willing and able to tolerate prophylactic anticoagulation.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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, 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, 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]

References

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

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

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

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Results from Two Consecutive Studies of Consolidation Therapy after Autologous Transplant for Multiple Myeloma: Thalidomide, Dexamethasone, and Clarithromycin or Lenalidomide, Dexamethasone, and Clarithromycin. [2018]

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

Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. [2022]

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

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

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

Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma. [2020]

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

Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. [2022]

8. England 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. [2018]

9. Spain pubmed.ncbi.nlm.nih.gov

Pomalidomide for patients with multiple myeloma. [2017]