IRD Regimen for Multiple Myeloma

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: Pregnancy, HIV, Hepatitis, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a three-drug regimen called IRD, designed to help people with multiple myeloma remain disease-free longer after a stem cell transplant. The treatment includes ixazomib, lenalidomide, and dexamethasone (a corticosteroid), with participants later receiving either ixazomib or lenalidomide as maintenance therapy. This trial may suit those with symptomatic multiple myeloma who have already undergone a stem cell transplant and completed at least two cycles of initial treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take other treatments for multiple myeloma during the study, except for corticosteroids if they are for other conditions.

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

Research shows that the combination of ixazomib, lenalidomide, and dexamethasone (IRD) is generally well-tolerated by people with multiple myeloma. This treatment is already used for patients whose cancer has returned or hasn't responded to previous treatments. Studies indicate it helps control the disease with manageable side effects.

Ixazomib alone might cause mild side effects like back pain or skin rashes. Lenalidomide can also lead to minor side effects, such as reduced appetite, which rarely results in weight loss.

Overall, studies have shown that the IRD treatment is safe for use in multiple myeloma. Most patients find the side effects manageable, and the treatment helps keep the disease under control. Discuss any concerns or questions about potential side effects with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they offer a targeted approach to therapy. The consolidation regimen combines ixazomib, lenalidomide, and dexamethasone, which work together to enhance the anti-cancer effects. Ixazomib is a proteasome inhibitor that disrupts cancer cell growth, and when used alongside lenalidomide and dexamethasone, it might improve patient outcomes by maintaining remission. The maintenance arms, using either ixazomib alone or lenalidomide, aim to prolong the period of remission with potentially fewer side effects compared to more intensive chemotherapy options. This approach is promising because it focuses on long-term disease management with targeted therapies.

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

Research has shown that the combination of ixazomib, lenalidomide, and dexamethasone, which participants in this trial may receive as part of the consolidation therapy, may effectively treat multiple myeloma. In earlier studies, patients using this combination experienced a 67% improvement in progression-free survival (PFS), meaning they went longer without their disease worsening. In this trial, some participants will receive ixazomib alone as part of Maintenance Arm 1, which showed that about 66% of patients had a positive response, with many seeing a significant reduction in their tumors. Others will receive lenalidomide alone as part of Maintenance Arm 2, which, when used continuously, helped keep the disease under control for over 10 months on average. These findings suggest that the IRD regimen could effectively delay the return of multiple myeloma after a stem cell transplant. ^{2 6 7 8 9}

Who Is on the Research Team?

Ravi Vij, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults aged 18-70 with symptomatic multiple myeloma, who've had initial therapy and are within 2-16 months of starting it. They must have good organ function, not be pregnant or breastfeeding, agree to contraception if applicable, and follow REMS program requirements for lenalidomide. Exclusions include other active cancers needing treatment, recent major surgery or serious infections, certain heart conditions, severe neuropathy among others.

Inclusion Criteria

Your blood and organ function should be within specific ranges, and you should not have received platelet transfusions within 7 days before the study.

I agree to follow the study's rules about preventing pregnancy.

I can take care of myself and perform daily activities.

Exclusion Criteria

I am not pregnant or breastfeeding.

I am scheduled for or have had two stem cell transplants using my own cells.

I do not have severe heart issues or uncontrolled blood pressure problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation

Participants receive four 28-day cycles of IRD (ixazomib, lenalidomide, and dexamethasone) following ASCT

16 weeks

Visits on Days 1, 8, and 15 of each cycle

Maintenance

Participants receive maintenance therapy with either ixazomib or lenalidomide until disease progression or unacceptable toxicity

Up to 5 years

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Ixazomib
• Lenalidomide

Trial Overview The trial is testing the IRD regimen (Ixazomib, Lenalidomide, Dexamethasone) after stem cell transplantation in multiple myeloma patients. Post four cycles of IRD treatment participants will randomly receive maintenance therapy with either Ixazomib or Lenalidomide to see which helps keep the disease at bay longer.

How Is the Trial Designed?

Group I: Maintenance Arm 2: Lenalidomide Experimental Treatment 1 Intervention

Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.

Group II: Maintenance Arm 1: Ixazomib Experimental Treatment 1 Intervention

Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity.

Group III: Consolidation: Ixazomib, Lenalidomide, & Dexamethasone Experimental Treatment 3 Interventions

Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, \& dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21.

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Published Research Related to This Trial

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

In two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

Dexamethasone remains a crucial part of multiple myeloma treatment, enhancing the effectiveness of novel therapies and improving response rates across all treatment phases.

New formulations of dexamethasone aim to reduce the number of pills patients need to take, which could help improve adherence to treatment and minimize medication errors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From mechanism to resistance - changes in the use of dexamethasone in the treatment of multiple myeloma. Rosenberg, AS.[2023]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

In a study of 44 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD) showed a significantly higher 1-year progression-free survival (PFS) rate of 45.5% compared to 31.8% for thalidomide and dexamethasone (TD).

Patients receiving BD also had a better overall survival rate at 3 years (70.0%) compared to those on TD (48.8%), although BD was associated with higher rates of certain adverse events like thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma. Iida, S., Wakabayashi, M., Tsukasaki, K., et al.[2021]

Lenalidomide, in combination with dexamethasone, was administered to 1438 patients with relapsed or refractory multiple myeloma, showing a median treatment duration of 15.4 weeks and confirming its efficacy in this patient population.

The most common adverse events included hematological issues (49%), gastrointestinal problems (59%), and fatigue (55%), with serious adverse events like pneumonia occurring in 8% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Chen, C., Reece, DE., Siegel, D., et al.[2021]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11596887/

Outcomes of Ixazomib Treatment in Relapsed and ... Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median ...

3. 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.

4. 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%) ...

5. myeloma.org myeloma.org/ninlaro-ixazomib

Ninlaro (ixazomib) Ninlaro continues to be studied in clinical trials as part of a wide spectrum of combination therapies and across myeloma disease settings.

6. ninlarohcp.com ninlarohcp.com/adverse-reactions

Safety Profile for the NINLARO ® (ixazomib) Regimen Avet-Loiseau H, Bahlis NJ, Chng W-J, et al. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. ...

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

A comparison of the efficacy and safety of ixazomib ... Another study showed that ixazomib combined with DXMS can also achieve a good outcome in treating incipient MM; the ORR of patients could reach 71%, and the ...

8. takedaoncology.com takedaoncology.com/news/news-releases/phase-3-trial-of-ninlarotm-ixazomib-as-first-line-maintenance-therapy-met-primary-endpoint-in-multiple-myeloma-patients-not-treated-with-stem-cell-transplantation/

Phase 3 Trial of NINLARO® (ixazomib) as First Line ... Results Demonstrated Statistically Significant Improvement in Progression-Free Survival -. - Data to be Submitted for Presentation at an Upcoming Medical ...

9. ninlaro.com ninlaro.com/multiple-myeloma-journey

Navigating Multiple Myeloma - NINLARO® (ixazomib) Rashes are common with NINLARO. NINLARO can cause rashes and other skin reactions that can be serious and can lead to death. Tell your healthcare provider right ...