Quad Regimen for Multiple Myeloma

Not currently recruiting at 12 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

Must be taking: Lenalidomide, Ixazomib, Daratumumab

Must not be taking: Strong CYP3A inducers

Disqualifiers: AL amyloidosis, Waldenström's, COPD, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to determine if they can help people with multiple myeloma, a type of blood cancer, live longer without disease progression. Participants will be randomly assigned to receive one of two drug regimens, both beginning with a combination of four medications, including Daratumumab Injection, followed by maintenance treatment. The trial seeks individuals newly diagnosed with multiple myeloma who are not eligible for high-dose chemotherapy with stem cell transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use certain medications like strong CYP3A inducers or St. John's wort within 14 days before starting the trial. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

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

Research has shown that the combination of lenalidomide, ixazomib, daratumumab, and dexamethasone has been tested for safety in several studies. One study found that this combination, particularly with ixazomib (a drug that blocks certain proteins in cancer cells), helps patients with relapsed multiple myeloma live longer. Another study found that even with low doses of dexamethasone, this combination was safe and could improve the quality of life for patients starting treatment.

Lenalidomide, often used with dexamethasone, has been shown to increase the chances of a positive response and help patients live longer compared to using dexamethasone alone. However, some patients experienced side effects, which were usually mild. It is important to know that, like any treatment, there can be risks, and some patients may need to stop due to side effects.

Overall, these treatments are generally well-tolerated, but patients should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Quad Regimen for multiple myeloma because it combines four powerful drugs—daratumumab, dexamethasone, ixazomib, and lenalidomide—offering a multi-faceted attack on cancer cells. Daratumumab is a monoclonal antibody that targets the CD38 protein on myeloma cells, while ixazomib is a proteasome inhibitor that disrupts cancer cell growth. This combination aims to enhance treatment effectiveness compared to the standard therapies, such as bortezomib-based regimens. With the potential to delay disease progression and manage symptoms more effectively, this regimen could represent a significant advancement in multiple myeloma treatment.

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

Research shows that a combination of four drugs—lenalidomide, ixazomib, daratumumab, and dexamethasone—may effectively treat multiple myeloma, a type of blood cancer. In this trial, one group of participants will receive this combination. Studies have found that this drug mix can lead to quick and positive results in patients. Specifically, one study showed that 53.5% of patients previously treated with daratumumab demonstrated at least minimal improvement with this combination. Another group in this trial will continue treatment with lenalidomide, ixazomib, and daratumumab, which studies suggest helps patients live longer. While lenalidomide alone has a 55% response rate in hard-to-treat cases, better treatments are still needed. Overall, this drug combination seems more effective than lenalidomide alone for treating multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Multiple Myeloma who can't have a stem cell transplant. They must not be pregnant, planning to become pregnant, or breastfeeding and agree to use two birth control methods if applicable. Participants need an ECOG score of 0-2 and meet specific health criteria without severe allergies or recent treatments that could interfere.

Inclusion Criteria

I have confirmed multiple myeloma with specific test results.

I agree to follow the pregnancy testing schedule as required.

I am using two reliable birth control methods or abstaining from sex.

Exclusion Criteria

I have not used any experimental drugs or devices recently.

I have COPD or asthma.

Pregnant, breast-feeding, planning to become pregnant, or planning to father a child during the study period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive 12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone

48 weeks

Weekly visits for drug administration

Maintenance

Participants receive maintenance therapy with lenalidomide, with or without ixazomib and daratumumab, until disease progression or unacceptable toxicity, for up to 2 years

Up to 2 years

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab Injection
• Dexamethasone
• Ixazomib
• Lenalidomide

Trial Overview The study tests whether adding ixazomib and daratumumab to lenalidomide maintenance therapy after initial treatment with these drugs plus dexamethasone improves patient outcomes. It's randomized: one group gets the full combo followed by just lenalidomide; the other continues all three drugs as maintenance.

How Is the Trial Designed?

Group I: Lenalidomide, Ixazomib, Daratumumab, and Dexamethasone Experimental Treatment 4 Interventions

12 cycles of lenalidomide, ixazomib, dexamethasone, and daratumumab followed by lenalidomide, ixazomib, and daratumumab until disease progression or unacceptable toxicity or a maximum of 2 year maintenance therapy.

Group II: Lenalidomide Experimental Treatment 4 Interventions

12 cycles of lenalidomide, ixazomib, daratumumab, and dexamethasone followed by lenalidomide until disease progression or unacceptable toxicity or a maximum of 2 years of maintenance therapy.

Who Is Running the Clinical Trial?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Takeda

Industry 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

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39966019/

Real-World Treatment Patterns and Outcomes in Patients ... Elderly patients with comorbidities and lenalidomide-refractory disease after 1 to 3 LOTs receive suboptimal regimens, have poor outcomes, and move rapidly ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924017647

Characteristics and outcomes in patients with lenalidomide ... Outcomes were suboptimal: 55 % response rate, 10-mo median PFS, and 28-mo median OS. •. New, effective therapies are needed for this difficult-to-treat ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01383-3/fulltext

A network meta-analysis of randomized clinical trials in ... Comparative efficacy of lenalidomide-free regimens in patients with relapsed/refractory multiple myeloma (RRMM) previously exposed to ...

4. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4320/487539/Characteristics-and-Outcomes-in-Patients-with

Characteristics and Outcomes in Patients with Lenalidomide ... The percent of patient indices with very good partial response or better was 29.0%, and the percent with complete response or better was 12.0%.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9972020/

Real‐world data on lenalidomide dosing and outcomes in ... The objective of our study was to understand the dosing, efficacy, and tolerability of lenalidomide among TI NDMM patients in the real‐world setting.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3256976/

Safety and Efficacy of Lenalidomide in Relapsed or ... Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone.

7. pharmacytimes.com pharmacytimes.com/view/discontinuing-lenalidomide-after-asct-may-be-safe-for-select-mrd-negative-patients-with-multiple-myeloma

Discontinuing Lenalidomide After ASCT May Be Safe for ... The safety outcomes were favorable, with 53% of patients experiencing at least 1 grade 1 or higher adverse event, and there were no ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00689936

NCT00689936 | Study to Determine Efficacy and Safety of ... The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose dexamethasone to that of the combination of melphalan, prednisone ...

9. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-ongoing-safety-review-revlimid-lenalidomide-and-possible-increased

Ongoing safety review of Revlimid (lenalidomide) and ... Data from evaluation of outcomes after long-term treatment also showed numerous second primary malignancies. Revlimid (lenalidomide) is approved ...