IRD Regimen for Multiple Myeloma

Recruiting at 44 trial locations

Overseen By Takeda Study Registration Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Millennium Pharmaceuticals, Inc.

Must be taking: Bortezomib, Lenalidomide, Dexamethasone

Must not be taking: CYP3A inducers

Disqualifiers: Other trials, Surgery, Cardiovascular, 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: 6

Duration: Up to 3 years

141 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim is to evaluate the effect of Ixazomib in combination with lenalidomide and dexamethasone on Multiple Myeloma disease progression at 2 years in participants who previously received a bortezomib-based induction regimen. The study will enroll approximately 160 participants, who are enrolled after completing 3 cycles of chemotherapy (Bortezomib-Based Induction Regimen). They are then treated with Ixazomib in addition to lenalidomide and dexamethasone.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong cytochrome P450 3A inducers like rifampin and St. John's wort, at least 14 days before starting the study drug. Other medications are not specifically mentioned, so it's best to discuss with your doctor.

What data supports the effectiveness of the drug regimen involving Dexamethasone, Ixazomib, and Lenalidomide for treating multiple myeloma?

Research shows that the combination of Ixazomib, Lenalidomide, and Dexamethasone is effective in treating relapsed and refractory multiple myeloma, with studies reporting significant response rates and improved survival outcomes. This drug regimen has been shown to be well-tolerated and effective even in patients who have undergone multiple previous treatments. ^{1 2 3 4 5}

Is the IRD regimen for multiple myeloma safe for humans?

The IRD regimen, which includes ixazomib, lenalidomide, and dexamethasone, has been shown to have a good safety profile in patients with multiple myeloma. Some studies report mild to moderate side effects, such as rash and peripheral neuropathy (nerve damage causing pain or numbness), but these are generally manageable. Serious side effects are rare, and the treatment is considered well-tolerated overall. ^{1 2 6 7 8}

What makes the IRD drug regimen unique for treating multiple myeloma?

The IRD regimen, which includes ixazomib, lenalidomide, and dexamethasone, is unique because it is an all-oral treatment option that has shown effectiveness and a good safety profile for patients with relapsed or refractory multiple myeloma, offering a convenient alternative to other regimens that may require injections or infusions. ^{1 2 3 9 10}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults with Multiple Myeloma who've had a bortezomib-based treatment but no disease progression. They should be ineligible for transplant or not planning one within 24 months, able to perform daily activities (ECOG status 0-2), and agree to use effective contraception.

Inclusion Criteria

Must be transplant ineligible as determined by their physician, or if transplant eligible, not expect to undergo transplant for at least 24 months after study enrollment.

I can take care of myself and am up and about more than half of my waking hours.

I am a woman who cannot become pregnant or will use two birth control methods during the study.

Exclusion Criteria

I do not have any uncontrolled heart problems.

I haven't taken specific strong medications or herbal supplements like St. John's wort in the last 14 days.

I haven't had any cancer besides nonmelanoma skin cancer or in situ carcinoma, or if I have, it was treated over 2 years ago with no remaining signs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ixazomib in combination with lenalidomide and dexamethasone in 28-day cycles until disease progression or unacceptable toxicity for up to 3 years

Up to 3 years

Multiple visits as per standard of care

Follow-up

Participants are monitored for progression-free survival and overall survival every 6 months after disease progression

Up to 2 years

Every 6 months

Treatment Details

Interventions

• Dexamethasone
• Ixazomib
• Lenalidomide

Trial Overview The study tests Ixazomib combined with Lenalidomide and Dexamethasone on patients who have completed prior chemotherapy. It aims to see how this combination affects the progression of Multiple Myeloma over two years in about 160 participants.

Participant Groups

Group I: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg Experimental Treatment 3 Interventions

Ixazomib 4 milligram (mg), capsules, orally, once, on Days 1, 8 and 15 and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21; and dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22 of a 28-day cycle for a maximum of 39 cycles until PD or unacceptable toxicity, whichever occurs first for up to 3 years.

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?

Millennium Pharmaceuticals, Inc.

Lead 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

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

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]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

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]

In a study involving 263 patients with relapsed/refractory multiple myeloma, the ixazomib-lenalidomide-dexamethasone (IRd) combination showed a high overall response rate of 73% and a median progression-free survival of 21.2 months, indicating its effectiveness in routine clinical practice.

However, the treatment also had notable safety concerns, with 17% of patients requiring dose reductions for ixazomib and 36% for lenalidomide, and 32% of patients discontinuing ixazomib and 30% discontinuing lenalidomide due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Hájek, R., Minařík, J., Straub, J., et al.[2021]

In a study of 52 newly diagnosed multiple myeloma patients, the Ixazomib/Lenalidomide/Dexamethasone (IRd) treatment showed similar efficacy to Bortezomib/Lenalidomide/Dexamethasone (VRd) in terms of progression-free survival and overall survival after 4 cycles of chemotherapy.

IRd demonstrated better safety, with a lower incidence of peripheral sensory neuropathy compared to VRd, making it a potentially more convenient option for patients with poorer health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib combined with lenalidomide and dexamethasone chemotherapy for newly diagnosed multiple myeloma in China-Compared with bortezomib/lenalidomide/dexamethasone. Huo, Z., Chen, F., Liu, P., et al.[2023]

References

1. 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]

2. 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]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. [2018]

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

Ixazomib, lenalidomide, and dexamethasone is effective and well tolerated in multiply relapsed (≥2nd relapse) refractory myeloma: a multicenter real world UK experience. [2021]

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

Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program. [2020]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. [2021]

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

Ixazomib combined with lenalidomide and dexamethasone chemotherapy for newly diagnosed multiple myeloma in China-Compared with bortezomib/lenalidomide/dexamethasone. [2023]