Ixazomib + Lenalidomide Maintenance Therapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: CYP1A2 inhibitors, CYP3A inhibitors

Disqualifiers: Pregnancy, Cardiovascular conditions, Infections, 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: 58

Duration: 24 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the safety of alternating ixazomib citrate and lenalidomide as treatment to help keep cancer from coming back after stem cell transplant (maintenance therapy) in treating patients with multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system to attack cancer cells. Giving ixazomib citrate and lenalidomide as maintenance therapy after transplant may prolong the length of time until the cancer returns.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong inhibitors or inducers of certain liver enzymes (like ciprofloxacin or rifampin) and supplements like Ginkgo biloba or St. John's wort, at least 14 days before starting the trial.

What data supports the effectiveness of the drug Ixazomib + Lenalidomide for Multiple Myeloma?

Research shows that the combination of ixazomib and lenalidomide significantly prolongs the time patients with multiple myeloma live without their disease getting worse. This combination has been effective in patients who have tried other treatments before, offering a new option for those with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

Is Ixazomib + Lenalidomide generally safe for humans?

Ixazomib, when used with lenalidomide and dexamethasone, has a good safety profile with manageable side effects, mainly including mild blood-related issues, digestive problems, or skin reactions. Common side effects reported include diarrhea, constipation, low blood platelet count, nerve damage, nausea, swelling, vomiting, and back pain. ^{1 6 7 8 9}

What makes the drug Ixazomib + Lenalidomide unique for multiple myeloma?

Ixazomib is unique because it is the first oral proteasome inhibitor used for multiple myeloma, making it more convenient compared to other treatments that require injections. When combined with lenalidomide, it offers a promising maintenance therapy option, especially for patients who have already undergone other treatments. ^{1 5 10 11 12}

Research Team

Leona Holmberg

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for multiple myeloma patients who've had a stem cell transplant using high dose melphalan therapy. They should be within 30-120 days post-transplant, recovered from acute toxicity, and have an ECOG performance status of 0-2. Participants must not be pregnant or breastfeeding, agree to contraception if of childbearing potential, and have adequate organ function. Exclusions include active infections, recent major surgery or radiotherapy, uncontrolled heart conditions, known allergies to study drugs or their components (including boron), certain prior cancers within 2 years except nonmelanoma skin cancer with complete resection.

Inclusion Criteria

You have enough infection-fighting white blood cells in your body.

I can take care of myself and perform daily activities.

Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria

I haven't taken specific strong medications or herbal supplements in the last 14 days.

I haven't had radiotherapy in the last 14 days, or if it was a small area, in the last 7 days.

Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alternating ixazomib citrate and lenalidomide as maintenance therapy after autologous transplant

24 months

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up at 30 days, then every 3 months

Treatment Details

Interventions

• Ixazomib Citrate
• Lenalidomide

Trial Overview The phase II trial tests alternating ixazomib citrate with lenalidomide as maintenance therapy after stem cell transplant in multiple myeloma patients. Ixazomib may block enzymes needed for cancer growth while lenalidomide might stimulate the immune system against cancer cells. The goal is to extend the time before the cancer returns.

Participant Groups

Group I: Treatment (ixazomib citrate and lenalidomide) Experimental Treatment 3 Interventions

Within 30-120 days after finishing autologous transplant, patients receive ixazomib citrate PO on days 1, 8 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-28. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients will continue to alternate between ixazomib citrate and lenalidomide every 2 courses for up to 24 months in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

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]

In a study of 90 patients with relapsed/refractory multiple myeloma, the combination of ixazomib, thalidomide, and dexamethasone showed a 51.1% overall response rate, indicating significant efficacy in treating this condition.

The treatment was well tolerated, with rare occurrences of severe toxicities, and ixazomib maintenance therapy improved response depth in 12.4% of patients, suggesting a beneficial long-term effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Ludwig, H., Poenisch, W., Knop, S., et al.[2021]

Continuous therapy, including the use of lenalidomide and bortezomib, has been effective in improving outcomes for both young and elderly patients with multiple myeloma due to their favorable safety profiles for long-term use.

Ixazomib, the first oral proteasome inhibitor, shows significant anti-myeloma activity both alone and in combination with other drugs, making it a promising candidate for maintenance therapy in multiple myeloma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ixazomib maintenance therapy in multiple myeloma. Offidani, M., Corvatta, L., Gentili, S., et al.[2016]

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. England pubmed.ncbi.nlm.nih.gov

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. [2021]

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

Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy. [2022]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

Ixazomib - lenalidomide - dexamethason in heavily pretreated multiple myeloma patients - case reports. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Oral ixazomib maintenance therapy in multiple myeloma. [2016]

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

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

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

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. [2023]

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

Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ixazomib maintenance therapy for patients with multiple myeloma: a meta-analysis. [2022]

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

Bortezomib Maintenance Therapy as a Standard of Care Provides Favorable Outcomes in Newly Diagnosed Myeloma Patients: A Multisite Real-Life Study. [2021]

12. 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]