Ibrutinib + Revlimid/Dexamethasone for Multiple Myeloma

Recruiting at 4 trial locations

Overseen By Quality Mangement and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: POEMS syndrome, Cardiovascular disease, Uncontrolled infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—ibrutinib (a cancer drug), lenalidomide (Revlimid), and dexamethasone (a corticosteroid)—to evaluate their effectiveness in treating multiple myeloma that has returned or not responded to previous treatments. The trial seeks to determine the optimal dose of these drugs for effective disease management. Participants who have experienced multiple myeloma symptoms and have not found success with other treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had certain treatments like high-dose corticosteroids or specific chemotherapy drugs within a certain period before joining the trial. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of ibrutinib, lenalidomide, and dexamethasone has been tested for safety in people with multiple myeloma, a type of blood cancer. In earlier studies, patients took these drugs together to assess their tolerability. Some experienced side effects, which is common with cancer treatments. The most reported issues included fatigue, low blood counts, and infections. However, many patients continued the treatment.

Testing these drugs together suggests potential effectiveness in treating multiple myeloma. Each drug is already used in cancer treatments, providing researchers with some knowledge about their safety. Although this is an early-stage study, with researchers still determining the best doses and possible side effects when used together, the ongoing research is promising and aims to optimize safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ibrutinib, Lenalidomide, and Dexamethasone for treating multiple myeloma because it targets the disease differently than standard treatments. While typical therapies often focus on killing cancer cells directly, Ibrutinib works by inhibiting a specific enzyme called Bruton's tyrosine kinase (BTK), which plays a crucial role in the survival and proliferation of cancer cells. This unique mechanism of action may offer a new way to combat multiple myeloma, potentially improving outcomes for patients who don't respond well to existing therapies. By combining Ibrutinib with Lenalidomide and Dexamethasone, researchers hope to enhance the treatment's effectiveness and overcome resistance to conventional options.

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

This trial will study the combination of ibrutinib, lenalidomide (Revlimid), and dexamethasone for treating relapsed or hard-to-treat multiple myeloma. Studies have shown that these drugs can be effective when used together. Research indicates that ibrutinib, combined with lenalidomide and dexamethasone, may reduce the ability of myeloma cells to survive and grow, thereby weakening the cancer cells. Early findings suggest this combination can help control the disease in patients unresponsive to other treatments. The goal is to improve outcomes by attacking the cancer cells in different ways. ^{1 3 4 5 6}

Who Is on the Research Team?

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Yvonne A. Efebera, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Jacob P. Laubach, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory multiple myeloma who have measurable disease, are in good physical condition (ECOG 0-1), and haven't progressed on high-dose lenalidomide. They must not have used ibrutinib or similar drugs before, be able to consent, follow the study plan, and provide samples for research. Pregnant women and those with certain health conditions are excluded.

Inclusion Criteria

Willingness to provide blood and tissue samples for correlative research purposes

My condition worsened after my last treatment.

Fertility requirements met

Exclusion Criteria

I have an infection with HIV, HCV, or HBV.

You have had certain syndromes and disorders in the past.

I have a serious liver condition that is affecting me now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Starting doses of ibrutinib and lenalidomide are assigned, with dose adjustments based on toxicity levels. Patients return every 28 days for assessments.

19 months

Monthly visits (in-person)

Dose Expansion

Additional patients are treated at the maximum tolerated dose determined in the dose escalation phase.

15 months

Monthly visits (in-person)

Follow-up

Participants are monitored for progression and survival endpoints after treatment.

34 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Ibrutinib
• Lenalidomide

Trial Overview The study tests a combination of Ibrutinib with Lenalidomide/Dexamethasone in men and women who've had at least one prior therapy for multiple myeloma. It's an open-label phase 1 trial where all participants receive the drug combo to evaluate its safety and effectiveness.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 3 Interventions

Dosage of the combination will depend on the determine of maximum tolerated dose learned from the Dose Escalation phase. Dose Expansion (Ibrutinib, Lenalidomide, Dexamethasone Combination)

Group II: Dose Escalation Experimental Treatment 3 Interventions

Dose escalation will consist of three different drug levels of Ibrutinib, Lenalidomide, and Dexamethasone. Dose Escalation (Ibrutinib, Lenalidomide, Dexamethasone Combination)

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Pharmacyclics LLC.

Industry Sponsor

Trials

114

Recruited

13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Published Research Related to This Trial

Ibrutinib, a novel oral treatment for multiple myeloma, showed a clinical benefit rate of 28% when combined with low-dose dexamethasone in patients who had undergone a median of 4 prior therapies, indicating its potential effectiveness in relapsed/refractory cases.

The study reported manageable safety profiles, with grade 3-4 adverse events occurring in a minority of patients, suggesting that ibrutinib could be a tolerable option for patients with multiple myeloma who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results. Richardson, PG., Bensinger, WI., Huff, CA., et al.[2021]

Lenalidomide, when combined with dexamethasone (Len/Dex), significantly improves overall survival in patients with relapsed or refractory multiple myeloma compared to dexamethasone alone, as shown in pivotal phase III trials.

Lenalidomide has a manageable safety profile with minimal neurotoxicity, making it suitable for long-term use, and is also effective as an induction therapy for newly diagnosed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. Dimopoulos, MA., Terpos, E., Niesvizky, R.[2013]

Lenalidomide, when combined with dexamethasone, has shown superior efficacy in treating relapsed multiple myeloma compared to dexamethasone alone, as demonstrated in two large phase III studies that reported improved response rates, progression-free survival, and overall survival.

The drug is administered orally in a 21-day cycle and has manageable side effects, such as neutropenia and venous thrombotic events, making it a viable treatment option for patients who have undergone at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United Kingdom myeloma forum position statement on the use of lenalidomide in multiple myeloma. Davies, F., Morris, C., Bird, J., 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 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 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]

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]

A subgroup analysis from two phase III clinical trials demonstrated that combining lenalidomide with dexamethasone is more effective than using dexamethasone alone for patients with relapsed or refractory multiple myeloma who had prior treatment with thalidomide.

This finding suggests that the lenalidomide and dexamethasone combination could be a more beneficial treatment option for these patients, potentially improving their outcomes in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. Meijer, E., Sonneveld, P.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12346632/

Ibrutinib in Combination with Lenalidomide Revlimid/ ... In vitro studies have demonstrated that treatment of myeloma cells with IBR results in a modest reduction in cell viability and the induction of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7496325/

Final analysis of a phase 1/2b study of ibrutinib combined ... This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM).

3. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/1912/427877/Phase-I-Trial-of-Ibrutinib-Lenalidomide-and

Phase I Trial of Ibrutinib, Lenalidomide and Dexamethasone ... We present safety and preliminary efficacy of the combination ibr, R, and dexamethasone (d) in RRMM patients. Methods: This is a phase I dose ...

4. mdpi.com mdpi.com/2072-6694/17/15/2433/review_report

Ibrutinib in Combination with Lenalidomide Revlimid ... This study presented a 3+3 phase I clinical trial of ibrutinib plus lenalidomide in R/R multiple myeloma and showed the combination of IBR with LEN and DEX was ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03015792?tab=results

No Study Results Posted | NCT03015792 | Ibrutinib, ... Ibrutinib, Lenalidomide, and Dexamethasone in Treating Patients With Multiple Myeloma Ineligible for Transplant. ClinicalTrials.gov ID ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03015792

Ibrutinib, Lenalidomide, and Dexamethasone in Treating ... This phase I/II trial studies the best dose and side effects of ibrutinib when given together with lenalidomide and dexamethasone and how well they work in ...