Ixazomib for Multiple Myeloma

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ixazomib citrate to evaluate its effectiveness for people with multiple myeloma, a type of blood cancer that has returned after treatment but remains sensitive to another drug, bortezomib. The goal is to determine if ixazomib citrate can inhibit cancer cell growth by blocking certain enzymes. Participants will receive various combinations of ixazomib citrate and other treatments, repeating every 28 days. Individuals whose multiple myeloma has recurred after treatment and who have already tried some standard treatments might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing 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 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.

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

A previous study found ixazomib citrate to be quite safe for treating multiple myeloma. Researchers discovered it did not cause long-term issues for patients. However, some experienced short-term side effects like diarrhea, affecting about 42% of patients in that study. Importantly, the FDA has already approved ixazomib for treating multiple myeloma, supporting its safety.

When combined with other drugs like cyclophosphamide and daratumumab, ixazomib remained safe. Studies suggest this combination did not add extra risks. Overall, ixazomib and its combinations are well-tolerated, meaning most people handle them well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ixazomib citrate for treating multiple myeloma because it offers a unique mechanism of action as a proteasome inhibitor, which disrupts cancer cell growth differently from traditional treatments like lenalidomide or bortezomib. Unlike typical treatments that are often administered intravenously, ixazomib citrate is given orally, making it more convenient for patients. Additionally, the various combinations with drugs like dexamethasone, cyclophosphamide, and daratumumab in the different arms of the study could potentially enhance its effectiveness, offering a tailored approach to tackling multiple myeloma. These factors make ixazomib citrate a promising and flexible option for patients, potentially improving outcomes and quality of life.

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

Research has shown that ixazomib citrate, one of the treatments in this trial, can be effective for people whose multiple myeloma has returned after treatment. In studies, patients using ixazomib combinations experienced a halt in disease progression for over 20 months. In this trial, some participants will receive ixazomib citrate with dexamethasone, which has yielded promising results, with many patients surviving at least six months. Another group will receive ixazomib citrate combined with cyclophosphamide and dexamethasone, which has also been effective in delaying disease progression. Additionally, a treatment arm combines ixazomib with daratumumab and cyclophosphamide, showing similar benefits. These findings suggest that ixazomib treatments can help control multiple myeloma and prevent it from worsening for a significant period. ^{2 6 7 8 9}

Who Is on the Research Team?

Shaji K. Kumar, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1.

ninlaro.com

ninlaro.com/clinical-studies

Results with NINLARO® (ixazomib)

In the clinical study, people taking the NINLARO treatment combination went more than a year and a half (20.6 months) without their multiple myeloma getting ...

2.

ninlarohcp.com

ninlarohcp.com/real-world-evidence

Real-World Evidence for the NINLARO® (ixazomib) Regimen

Real-world and clinical trial data in relapsed/refractory multiple myeloma (RRMM): Evaluating treatment duration and comparing effectiveness and efficacy.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4189713/

An evidence-based review of ixazomib citrate and its ...

With a median follow-up of 7 months, overall survival (OS) at 6 months was 96%. After these Phase I and II studies showed activity of the single-agent ixazomib ...

4.

myeloma.org

myeloma.org/ninlaro-ixazomib

Ninlaro (ixazomib)

The FDA stated that it is not recommended in the maintenance setting or in newly diagnosed myeloma in combination with Rd outside of controlled clinical trials.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10344838/

Real-world effectiveness of ixazomib combined with ...

mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older (p = 0.06) with similar ORR (72.4% and 76.8%) ...

6.

ninlarohcp.com

ninlarohcp.com/adverse-reactions

Safety Profile for the NINLARO ® (ixazomib) Regimen

Limitations of Use: NINLARO is not recommended for use in the maintenance setting or in newly diagnosed multiple myeloma in combination with lenalidomide and ...

7.

ninlaro.com

ninlaro.com/sites/default/files/resources/ninlaro-prescribing-information.pdf

Prescribing Information for NINLARO® (ixazomib)

Ixazomib induced apoptosis of multiple myeloma cell lines in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5574012/

Management of adverse events associated with ixazomib ...

Based on pharmacokinetic and safety data, a reduced ixazomib starting dose of 3·0 mg is recommended in patients with severe renal impairment or end‐stage renal ...

9.

ema.europa.eu

ema.europa.eu/en/documents/product-information/ninlaro-epar-product-information_en.pdf

Ninlaro, INN-ixazomib citrate - EMA

Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, ...