Ixazomib for Multiple Myeloma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CYP3A inducers

Disqualifiers: Recent chemotherapy, Other malignancy, Cardiovascular conditions, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 2.5 years

165 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well ixazomib citrate works in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) but is not resistant to bortezomib (refractory). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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 take certain medications like strong inhibitors of CYP3A or use Ginkgo biloba or St. John's wort within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ixazomib for treating multiple myeloma?

Research shows that Ixazomib, when combined with lenalidomide and dexamethasone, significantly extends the time patients with relapsed or refractory multiple myeloma live without their disease getting worse. This combination also results in a higher overall response rate compared to a placebo, making it an effective treatment option. ^{1 2 3 4 5}

What makes the drug Ixazomib unique for treating multiple myeloma?

Ixazomib is unique because it is the first proteasome inhibitor (a type of drug that blocks protein breakdown in cells) that can be taken orally, making it more convenient compared to other similar treatments that require injections. ^{1 2 3 6 7}

Research Team

Shaji K. Kumar, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for patients with relapsed multiple myeloma who are not resistant to bortezomib. They should have recovered from previous treatments, have adequate organ function, and no severe concurrent illnesses. Those with certain infections or a recent history of other cancers (except nonmelanoma skin cancer) are excluded.

Inclusion Criteria

Willing to return to consenting Mayo Clinic institution for follow-up during the Active Monitoring Phase of the study; Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up

I have recovered from side effects of my previous cancer treatment.

My kidney function, measured by creatinine clearance, is adequate.

Exclusion Criteria

You have hepatitis B or active hepatitis C infection.

I am HIV positive.

This criterion refers to a list of specific conditions or factors that will be mentioned in the following text.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib citrate with or without additional drugs depending on the arm, in cycles of 28 days

2.5 years

Visits on days 1, 8, 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 or 12 months

Treatment Details

Interventions

• Ixazomib Citrate

Trial Overview The study tests ixazomib citrate's effectiveness in treating relapsed multiple myeloma when it's not refractory to bortezomib. It includes dexamethasone, cyclophosphamide, daratumumab, and lab biomarker analysis to see if the drug can halt cancer cell growth by blocking key enzymes.

Participant Groups

Group I: Arm E (ixazomib citrate, cyclophosphamide, daratumumab) Experimental Treatment 5 Interventions

Patients receive ixazomib citrate PO on days 1, 8, and 15, cyclophosphamide PO (cycles 1-12 only) on days 1, 8, 15, 22, and daratumumab IV on days 1, 8, 15, 22 (cycles 1-2), days 1 and 15 (cycles 3-6), and day 1 in all subsequent cycles. Patients also receive dexamethasone IV or PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide) Experimental Treatment 4 Interventions

Patients receive ixazomib citrate PO on days 1, 8, and 15 and cyclophosphamide PO (cycles 1-18 only) and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: Arm C (higher-dose ixazomib citrate and dexamethasone) Experimental Treatment 3 Interventions

Patients receive higher doses of ixazomib citrate PO on days 1, 8, and 15 and dexamethasone PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group IV: Arm B (ixazomib citrate and dexamethasone) Experimental Treatment 3 Interventions

Patients receive ixazomib citrate PO on days 1, 8, and 15 and dexamethasone PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group V: Arm A (ixazomib citrate and dexamethasone, closed to accrual) Experimental Treatment 3 Interventions

Patients receive ixazomib citrate PO on days 1, 8, and 15. Patients with lack of minor response by the end of the second cycle or lack of partial response by the end of the fourth cycle also receive dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ixazomib Citrate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ninlaro for:

• Multiple myeloma

Approved in United States as Ninlaro for:

• Multiple myeloma

Approved in Canada as Ninlaro for:

• Multiple myeloma

Approved in Japan as Ninlaro for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

Ixazomib, an oral proteasome inhibitor, has been shown to significantly improve progression-free survival in patients with relapsed and/or refractory multiple myeloma when combined with lenalidomide and dexamethasone, with a median survival of 20.6 months compared to 14.7 months for the placebo group.

The drug works by selectively inhibiting the 20S proteasome, leading to the accumulation of proteins that induce stress and apoptosis in myeloma cells, making it a promising treatment option for patients who have undergone prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. Machida, M., Fukunaga, S., Hara, T.[2019]

Ixazomib is an orally taken proteasome inhibitor that works by blocking the β5 subunit of the proteasome, and it was approved by the FDA in 2015 for treating multiple myeloma in combination with lenalidomide and dexamethasone after at least one prior therapy.

Currently, ixazomib is being studied in Phase III trials for newly diagnosed multiple myeloma and other conditions, indicating its potential for broader applications in treating various cancers and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. Shirley, M.[2018]

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. France pubmed.ncbi.nlm.nih.gov

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

2. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. [2019]

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

Ixazomib: First Global Approval. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Safety of ixazomib for the treatment of multiple myeloma. [2017]

5. 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]

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

Ixazomib for the treatment of multiple myeloma. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Ixazomib in the management of relapsed multiple myeloma. [2019]