IRD Regimen for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment combination for multiple myeloma, a type of blood cancer. The treatment includes three drugs: ixazomib, lenalidomide, and dexamethasone (also known as Decadron, Dexone, or Hexadrol). Researchers aim to determine if this combination slows the disease over two years. Suitable participants have completed three cycles of a specific chemotherapy (bortezomib-based) without disease progression and do not plan on a transplant soon. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand its benefits for more patients.

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 is the safety track record for the IRD regimen treatments?

Research has shown that the combination of ixazomib, lenalidomide, and dexamethasone is generally well-tolerated by people with multiple myeloma. In one study, patients using these drugs together experienced over a year and a half without disease progression, suggesting the treatment's effectiveness without major issues. Another study found that adding ixazomib to lenalidomide and dexamethasone significantly extended the time patients lived without cancer progression.

These studies indicate that the treatment is safe enough for long-term use in many cases. However, like any medication, some individuals may experience side effects. Discussing potential risks and benefits with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the IRD regimen for multiple myeloma because it combines three drugs—Ixazomib, Lenalidomide, and Dexamethasone—in a novel way that could enhance treatment effectiveness. Ixazomib is a proteasome inhibitor that is taken orally, which is more convenient than the intravenous administration required for many existing treatments. This regimen could offer a more patient-friendly option by reducing the need for hospital visits. Additionally, combining these drugs may result in a synergistic effect, potentially leading to better outcomes compared to using each drug separately.

What is the effectiveness track record for the IRD regimen in treating Multiple Myeloma?

Research has shown that the combination of ixazomib, lenalidomide, and dexamethasone, which participants in this trial will receive, effectively treats multiple myeloma. Studies indicate that people on this treatment can remain progression-free for over a year and a half (20.6 months). This combination helps patients live longer without disease progression and is generally well-tolerated, with most patients not experiencing severe side effects. This treatment is particularly promising for those who have already tried other therapies, such as bortezomib. ^{2 3 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

Citations

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

Real-world effectiveness of ixazomib combined with ... Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study. M ...

2. 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 ...

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

Outcomes of Ixazomib Treatment in Relapsed and ... Our study demonstrates that ixazomib, used in combination with lenalidomide, dexamethasone, or other options, is an effective and well-tolerated ...

4. 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.

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. 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 ...

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.