Ixazomib Combo for Multiple Myeloma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Joseph Tuscano

Must not be taking: Clarithromycin, Strong CYP inhibitors

Disqualifiers: Pregnancy, Cardiovascular conditions, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and understand the side effects of a new treatment combination for people with multiple myeloma, a type of blood cancer. It evaluates how well clarithromycin, ixazomib citrate (a proteasome inhibitor), pomalidomide, and dexamethasone work together to stop cancer cell growth and boost the immune system. The trial seeks participants who have not responded to previous treatments with specific drugs and have a confirmed diagnosis of multiple myeloma. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking clarithromycin, anti-myeloma therapy, or plasmapheresis within 30 days before starting the study. Additionally, you cannot use strong inhibitors or inducers of certain liver enzymes (CYP1A2 and CYP3A) within 14 days before the first dose of study drugs.

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

Research shows that combining ixazomib with pomalidomide and dexamethasone may help treat multiple myeloma, a type of blood cancer. Studies have found that the FDA has approved ixazomib for use with other drugs for this cancer, indicating its general safety. Adding clarithromycin might enhance the treatment's effectiveness due to its cancer-fighting properties.

Most participants who took these drugs together tolerated them well, though some experienced side effects. Common side effects included fatigue, low blood cell counts, and nausea. Serious side effects were less common. As this trial is in its early stages, the goal is to determine the best dose and closely monitor side effects. Participants will receive careful monitoring to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combo of Ixazomib Citrate, Pomalidomide, Clarithromycin, and Dexamethasone for multiple myeloma because it brings a novel approach to tackling the cancer. Unlike the standard of care, which often involves proteasome inhibitors like bortezomib and immunomodulatory drugs such as lenalidomide, this combination leverages ixazomib as an oral proteasome inhibitor, potentially offering improved convenience and adherence. Additionally, pomalidomide is included as a newer-generation immunomodulatory drug, which may enhance immune response against the cancer cells. This blend of mechanisms aims to provide a more effective and patient-friendly treatment option for those battling multiple myeloma.

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

In this trial, participants will receive a combination treatment of ixazomib citrate, pomalidomide, clarithromycin, and dexamethasone. Research has shown that ixazomib citrate effectively treats multiple myeloma, with patients experiencing over 20 months without cancer progression. Pomalidomide has also proven effective, with about 36% of patients showing significant improvement. Clarithromycin, when combined with other treatments, has increased success rates for multiple myeloma patients. Dexamethasone alone has a success rate of 50-60% in treating myeloma. Together, these treatments offer promise, especially when other therapies have failed. ^{6 7 8 9 10}

Who Is on the Research Team?

Joseph M. Tuscano

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that's gotten worse after treatment. They must have had a biopsy confirming the diagnosis, measurable disease, and be in fairly good health (ECOG status 0-2). Participants need to agree to use contraception and should not have other serious illnesses or recent treatments that could affect the study drugs' absorption or their own recovery.

Inclusion Criteria

I have been cancer-free for over 5 years, except for nonmelanoma skin cancer or carcinoma in situ which was fully removed.

I am following the required birth control measures.

Voluntary written consent

Exclusion Criteria

I am not pregnant or breastfeeding.

I have not had major surgery in the last 14 days.

I have not had radiotherapy in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pomalidomide, ixazomib citrate, clarithromycin, and dexamethasone in 28-day cycles for 6 courses

24 weeks

Visits on days 1, 8, 15, and 22 of each cycle

Maintenance Therapy

Participants continue to receive pomalidomide, ixazomib citrate, and dexamethasone with clarithromycin in 28-day cycles

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 2-3 months

What Are the Treatments Tested in This Trial?

Interventions

• Clarithromycin
• Dexamethasone
• Ixazomib Citrate
• Pomalidomide

Trial Overview The trial is testing clarithromycin combined with ixazomib citrate, pomalidomide, and dexamethasone on patients whose multiple myeloma has resisted previous treatments. It aims to find the safest dose of clarithromycin when used with these drugs and see how well this combination works against cancer cells.

How Is the Trial Designed?

Group I: Treatment (PiC-D therapy) Experimental Treatment 4 Interventions

Patients receive pomalidomide PO QD on days 1-21; ixazomib citrate PO on days 1, 8, and 15; clarithromycin PO BID on days 15-21 of course 1 and days 1-21 of courses 2-6; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pomalidomide, ixazomib citrate, and dexamethasone as above and receive clarithromycin PO BID or QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Joseph Tuscano

Lead Sponsor

Trials

8

Recruited

180+

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

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

Ixazomib, an oral proteasome inhibitor, significantly prolongs progression-free survival (PFS) in patients with relapsed and/or refractory multiple myeloma compared to placebo, as demonstrated in the TOURMALINE-MM1 trial involving adults who had received one to three prior therapies.

The treatment showed a favorable safety profile and resulted in a higher overall response rate, making ixazomib a valuable new option for patients with multiple myeloma who have undergone previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. Al-Salama, ZT., Garnock-Jones, KP., Scott, LJ.[2018]

In a phase II study involving 30 patients with relapsed and refractory myeloma, a combination of clarithromycin, low-dose thalidomide, and low-dose dexamethasone was well tolerated and effective, with a 96% overall response rate.

The combination therapy led to high response rates, with 89% of patients achieving at least a 50% reduction in paraprotein levels, demonstrating that this approach allows for lower and more tolerable doses of the medications while still providing significant clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. Morris, TC., Kettle, PJ., Drake, M., et al.[2022]

In a study involving 43 East Asian patients with relapsed/refractory multiple myeloma, the oral proteasome inhibitor ixazomib was found to be rapidly absorbed and had a recommended phase 2/3 dose of 4.0 mg, with no dose-limiting toxicities reported.

The combination of ixazomib with lenalidomide and dexamethasone showed promising efficacy, with 65% of response-evaluable patients achieving at least a partial response, indicating that this treatment regimen is both active and well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. Gupta, N., Goh, YT., Min, CK., et al.[2019]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4390045/

Clarithromycin overcomes resistance to lenalidomide and ... The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led to highly durable responses in newly diagnosed myeloma.

2. journals.lww.com journals.lww.com/egjh/fulltext/2024/07000/impact_of_adding_clarithromycin_in_multiple.17.aspx

Impact of adding clarithromycin in multiple myeloma... The main purpose of this two-arm prospective interventional study was to assess the effect of adding clarithromycin to the standard-of-care chemotherapeutic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02573935

Clarithromycin in Multiple Myeloma Induction Therapy This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3596960/

BiRd (clarithromycin, lenalidomide, dexamethasone) Long-term lenalidomide/dexamethasone/biaxin in newly diagnosed myeloma is safe and effective. No increased incidence of second primary malignancies seen in ...

5. ashpublications.org ashpublications.org/ashclinicalnews/news/4864/Clarithromycin-Improves-Responses-But-Fails-to

Clarithromycin Improves Responses But Fails to Prolong ... Adding the antibiotic clarithromycin to lenalidomide plus dexamethasone improved the response rate in patients with multiple myeloma (MM), compared with ...

6. 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. Detailed Description.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4714737/

Spotlight on ixazomib: potential in the treatment of multiple ... Ixazomib is the first oral boronic acid-based PI approved by US FDA in combination with lenalidomide and dexamethasone for the treatment of MM ...

8. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT02542657

UCSD Myeloma Trial → Ixazomib with Pomalidomide ... Giving clarithromycin with ixazomib citrate, pomalidomide and dexamethasone may be a better treatment for patients with multiple myeloma. SHOW ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40948663/

Clarithromycin, ixazomib, pomalidomide, dexamethasone ... Clarithromycin is a macrolide antibiotic with anti-multiple myeloma (MM) activity when combined with dexamethasone and immunomodulatory agents.

10. nature.com nature.com/articles/s41375-019-0384-1

Ixazomib, lenalidomide, and dexamethasone in patients ... We examined the long-term efficacy and safety of the all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd), followed by single-agent ...