Ixazomib Combo for Multiple Myeloma

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of clarithromycin when given together with ixazomib citrate, pomalidomide, and dexamethasone and to see how well it works in treating patients with multiple myeloma that has not responded to previous treatment. Biological therapies, such as clarithromycin, pomalidomide, and dexamethasone, use substances made from living organisms that may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clarithromycin with ixazomib citrate, pomalidomide and dexamethasone may be a better treatment for patients with multiple myeloma.

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.

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

Research shows that ixazomib, when combined with other drugs like dexamethasone, is effective in treating multiple myeloma, with a significant number of patients experiencing a positive response. Additionally, clarithromycin combined with dexamethasone has shown effectiveness in similar treatments, suggesting potential benefits in this combination. ^{1 2 3 4 5}

Is the Ixazomib combination treatment generally safe for humans?

The combination of ixazomib, pomalidomide, and dexamethasone has been studied in patients with relapsed or refractory multiple myeloma and is generally well-tolerated. Common side effects include anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count), but these are manageable. Peripheral neuropathy (nerve damage) was infrequent, indicating the treatment is relatively safe for human use. ^{3 5 6 7 8}

What makes the Ixazomib Combo drug unique for treating multiple myeloma?

The Ixazomib Combo drug is unique because it includes ixazomib, the first oral proteasome inhibitor, which allows for an all-oral treatment regimen. This combination is designed to be effective and convenient for patients with multiple myeloma, especially those who have relapsed or are refractory to other treatments. ^{1 2 4 8 9}

Research Team

Joseph M. Tuscano

Principal Investigator

University of California, Davis

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma. [2019]

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

Comparison between ixazomib+cyclophosphamide+dexamethasone regimen and ixazomib+dexamethasone regimen for elderly and frail patients having newly diagnosed multiple myeloma. [2023]

3. 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]

4. France pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

5. 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]

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

Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. [2022]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Phase I/II trial of the oral regimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. [2019]