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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug combination to prevent multiple myeloma, a type of blood cancer, from returning after a stem cell transplant. The treatment alternates between ixazomib (Ninlaro), which may stop cancer cell growth, and lenalidomide (Revlimid), which can help the immune system fight cancer. This trial may suit those who have undergone a stem cell transplant for multiple myeloma and have recovered from the procedure's immediate effects. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research has shown that the combination of ixazomib citrate and lenalidomide has been tested for safety in patients with multiple myeloma. Earlier studies found this combination to be generally well-tolerated, with patients experiencing a longer period before the disease worsened.

Real-world studies and clinical trials have found that adding ixazomib to lenalidomide maintenance therapy did not cause any unexpected side effects. This allows patients to continue treatment with manageable side effects. Common side effects reported in these studies included nausea, diarrhea, and fatigue, but these were usually mild to moderate.

Both drugs have been used previously to treat multiple myeloma, so their safety is well understood. This ensures that doctors know how to manage any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ixazomib citrate and lenalidomide for multiple myeloma because it offers a novel maintenance therapy approach. Unlike standard treatments that often require more frequent hospital visits, ixazomib is an oral proteasome inhibitor that patients can take at home, potentially making it more convenient and less disruptive to daily life. Additionally, this combination targets the cancer cells in a way that may enhance the body's immune response, which might lead to longer remission periods compared to existing therapies. Overall, this regimen could represent a significant step forward in maintaining remission with fewer side effects and more ease for patients.

What evidence suggests that ixazomib citrate and lenalidomide could be effective for multiple myeloma?

Research has shown that using ixazomib citrate with lenalidomide can help manage multiple myeloma, a type of blood cancer. In this trial, participants will receive alternating courses of ixazomib citrate and lenalidomide as maintenance therapy. Studies have found that adding ixazomib to lenalidomide can extend the time before the cancer worsens, with some patients experiencing over 18 months without progression. This combination has also been linked to higher rates of complete remission, meaning the cancer is not detectable after treatment. Additionally, this treatment approach has proven effective and aligns with real-world results. These findings suggest that using ixazomib citrate and lenalidomide as ongoing therapy might help prevent the cancer from returning after a stem cell transplant. ^{1 4 5 6 7}

Who Is on the Research Team?

Leona Holmberg

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8205687/

A comparison of the efficacy and safety of ixazomib ...

Conclusion: Compared with the combination of lenalidomide and DXMS, ixazomib combined with DXMS can achieve higher complete remission rate and more improved PFS ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1516282

Oral Ixazomib, Lenalidomide, and Dexamethasone for ...

The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival.

3.

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 ...

4.

pmc.ncbi.nlm.nih.gov

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

Real-world effectiveness of ixazomib combined with ...

Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03173092

NCT03173092 | A Study of Ixazomib (NINLARO®) in ...

This study will look at the effectiveness and safety in participants who take the all-oral combination of ixazomib added to lenalidomide and dexamethasone.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34992070/

Safety and Efficacy of Combination Maintenance Therapy with ...

Conclusions: The addition of ixazomib to lenalidomide maintenance demonstrated a better than expected PFS compared with historical data using ...

7.

ninlarohcp.com

ninlarohcp.com/real-world-evidence

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

The NINLARO® regimen has been investigated in patients with relapsed multiple myeloma in both randomized controlled trials and real-world studies.