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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Ibrutinib, Lenalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Ibrutinib, Lenalidomide, and Dexamethasone is safe and well-tolerated, with a clinical benefit rate of 80% in patients with relapsed or refractory multiple myeloma. Additionally, Lenalidomide and Dexamethasone together have been shown to be effective in improving survival and response rates in multiple myeloma patients. ^{1 2 3 4 5}

Is the combination of Ibrutinib, Lenalidomide, and Dexamethasone safe for treating multiple myeloma?

The combination of Ibrutinib, Lenalidomide, and Dexamethasone has been studied for safety in patients with multiple myeloma. Common side effects include blood-related issues like anemia (low red blood cells), neutropenia (low white blood cells), and thrombocytopenia (low platelets), as well as rash and infections. Overall, this combination appears to be safe and well-tolerated, with manageable side effects in heavily pretreated patients. ^{1 2 6 7 8}

What makes the drug combination of Ibrutinib, Lenalidomide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it includes Ibrutinib, a first-in-class oral inhibitor targeting Bruton tyrosine kinase, which is overexpressed in multiple myeloma cells, offering a novel mechanism of action. The combination with Lenalidomide and Dexamethasone aims to enhance efficacy in patients who have relapsed or are resistant to other treatments, providing a new option for heavily pretreated patients. ^{1 2 9 10 11}

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

Eligibility Criteria

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

I am 18 years old or older.

My condition worsened after my last treatment.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: Phase I trial results. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. [2021]

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

Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. [2018]

5. 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]

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

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

7. England pubmed.ncbi.nlm.nih.gov

United Kingdom myeloma forum position statement on the use of lenalidomide in multiple myeloma. [2018]

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-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. [2021]

10. 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]

11. Netherlands pubmed.ncbi.nlm.nih.gov

How lenalidomide is changing the treatment of patients with multiple myeloma. [2013]