IRD Regimen for Multiple Myeloma

Recruiting at 9 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

236 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.

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.

What evidence supports the effectiveness of the IRD regimen for treating multiple myeloma?

Research shows that dexamethasone, a key component of the IRD regimen, has been effective in treating multiple myeloma when combined with other drugs, improving response rates and outcomes. Additionally, studies have demonstrated that dexamethasone enhances the effectiveness of other treatments in patients with relapsed or resistant multiple myeloma. ^{1 2 3 4 5}

Is the IRD regimen for multiple myeloma generally safe for humans?

The IRD regimen, which includes lenalidomide and dexamethasone, has been studied for safety in multiple myeloma patients. Common side effects include fatigue, muscle cramps, rash, and infections, with some serious effects like pneumonia and blood clots. These treatments are generally well-tolerated, but monitoring for side effects is important. ^{3 6 7 8 9}

How does the IRD regimen for multiple myeloma differ from other drug treatments?

The IRD regimen, which includes ixazomib, lenalidomide, and dexamethasone, is unique because it combines these three drugs to treat relapsed or refractory multiple myeloma, offering a balance of effectiveness and safety. This combination is particularly noted for its use in Asian patients, where real-world data on its safety and effectiveness are limited. ^{5 10 11 12 13}

Research Team

Ravi Vij, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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 have been diagnosed with symptomatic multiple myeloma.

Exclusion Criteria

I am not pregnant or breastfeeding.

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

I am not planning to receive any other cancer treatments until 28 days after my transplant.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Combination of interferon and dexamethasone in refractory multiple myeloma. [2019]

3. Italy 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. [2022]

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

Effective treatment of advanced multiple myeloma refractory to alkylating agents. [2015]

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

A phase I/II study of idarubicin, dexamethasone and interferon-alpha (I-Dexa) in patients with relapsed or refractory multiple myeloma. [2018]

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

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

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

Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. [2021]

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

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

9. Greece 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. [2015]

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

Comparison between ixazomib+cyclophosphamide+dexamethasone regimen and ixazomib+dexamethasone regimen for elderly and frail patients having newly diagnosed multiple myeloma. [2023]

11. Japan pubmed.ncbi.nlm.nih.gov

Real-world toxicity and effectiveness of ixazomib, lenalidomide, and dexamethasone in Korean patients with relapsed and/or refractory multiple myeloma. [2023]

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

Primary dexamethasone treatment of multiple myeloma. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma. [2021]