What is the mechanism of action of this treatment?

BTK inhibitors, such as ibrutinib, block Bruton's tyrosine kinase, a key enzyme in the signaling pathways that promote the growth and survival of myeloma cells. Immunomodulatory drugs (IMiDs) like lenalidomide enhance the immune system's ability to attack myeloma cells, inhibit angiogenesis (formation of new blood vessels that supply the tumor), and directly induce myeloma cell death. Corticosteroids, such as dexamethasone, reduce inflammation and have direct anti-myeloma effects by inducing apoptosis (programmed cell death) in myeloma cells. These mechanisms are crucial for Multiple Myeloma patients as they target the disease through different pathways, improving treatment efficacy and potentially leading to better outcomes.

What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma involving lenalidomide and dexamethasone, often combined with other agents, have a range of side effects. Lenalidomide can cause neutropenia, thrombocytopenia, infections, venous thromboembolism, and gastrointestinal issues such as diarrhea and constipation. Dexamethasone, a corticosteroid, can lead to hyperglycemia, increased risk of infections, insomnia, and mood changes. When combined with other agents like bortezomib or cyclophosphamide, additional side effects may include peripheral neuropathy, fatigue, and increased risk of venous thromboembolism. BTK inhibitors like ibrutinib can cause bleeding, infections, and cardiac issues such as atrial fibrillation. It is important to monitor these side effects closely and manage them in consultation with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Myeloma, particularly those involving immunomodulatory drugs and corticosteroids. Lenalidomide, an immunomodulatory drug, in combination with dexamethasone, has been a cornerstone in Multiple Myeloma treatment. Additionally, combinations like Bortezomib (a proteasome inhibitor) with lenalidomide and dexamethasone (VRd) have shown significant efficacy and are widely used. While Ibrutinib, a BTK inhibitor, is being studied in combination with lenalidomide and dexamethasone, it is not yet a standard approved regimen for Multiple Myeloma. Other notable FDA-approved combinations include Carfilzomib with dexamethasone and Daratumumab with lenalidomide and dexamethasone.

What other types of research exist?

Promising novel alternatives for Multiple Myeloma treatment include: <ol> <li>Isatuximab-based therapies, such as Isatuximab with Carfilzomib and Dexamethasone.</li> <li></li> </ol> Belantamab mafodotin, particularly for relapsed or refractory cases. 3. Teclistamab, a bispecific antibody showing promise in relapsed or refractory Multiple Myeloma. 4. Selinexor-based regimens, such as Selinexor with Bortezomib and Dexamethasone. 5. Panobinostat in combination with Bortezomib and Dexamethasone. These alternatives have shown efficacy in recent clinical trials and may offer new options for patients in 2024.

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Corticosteroid

Ibrutinib + Revlimid/Dexamethasone for Multiple Myeloma

Phase 1

Waitlist Available

Led By Suzanne George, MD

Research Sponsored by Alliance Foundation Trials, LLC.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At least 1 prior therapy with demonstrated disease progression following the most recent line of treatment

Progression of disease within 60 days of completion of last therapeutic regimen or failure to achieve minimal response while on last treatment

Must not have

Known infection with HIV, HCV, or HBV

Currently active, clinically significant hepatic impairment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 34 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs in patients whose multiple myeloma has returned or did not respond to previous treatments. The drugs work by blocking cancer cell growth, boosting the immune system, and reducing inflammation. The study aims to find the safest and most effective dose of these drugs.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include risk of bleeding, infections due to lowered immunity from Dexamethasone; heart issues or liver problems from Ibrutinib; and blood clots or kidney damage from Lenalidomide. Side effects vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after my last treatment.

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My condition worsened within 2 months after my last treatment.

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My blood counts are healthy without needing transfusions or medications to help.

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I am not pregnant.

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I am fully active or can carry out light work.

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I have symptoms from my multiple myeloma, which can be measured.

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My condition did not worsen while on lenalidomide doses over 10mg.

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I have not taken ibrutinib or drugs targeting B-cell signals.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have a known bleeding disorder.

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I have not had major surgery in the last 4 weeks.

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My diabetes is not well-managed.

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I have a heart condition that affects my daily life.

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I have an ongoing infection that is not under control.

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I have lingering side effects from previous cancer treatments.

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I cannot swallow pills or have a major stomach condition.

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I do not have any severe illnesses or conditions that could threaten my life.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 34 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~34 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 34 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose for Combination

Objective Response Rate

Secondary study objectives

Duration of Response

Maximum Toxicity Grade

Overall Survival

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose ExpansionExperimental Treatment3 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 EscalationExperimental Treatment3 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

Lenalidomide

2005

Completed Phase 3

~2240

Dexamethasone

2007

Completed Phase 4

~2650

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

BTK inhibitors, such as ibrutinib, block Bruton's tyrosine kinase, a key enzyme in the signaling pathways that promote the growth and survival of myeloma cells. Immunomodulatory drugs (IMiDs) like lenalidomide enhance the immune system's ability to attack myeloma cells, inhibit angiogenesis (formation of new blood vessels that supply the tumor), and directly induce myeloma cell death. Corticosteroids, such as dexamethasone, reduce inflammation and have direct anti-myeloma effects by inducing apoptosis (programmed cell death) in myeloma cells. These mechanisms are crucial for Multiple Myeloma patients as they target the disease through different pathways, improving treatment efficacy and potentially leading to better outcomes.