Palbociclib + Ibrutinib for Mantle Cell Lymphoma

Recruiting at 8 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

Must be taking: Palbociclib, Ibrutinib

Must not be taking: CYP3A inhibitors, inducers

Disqualifiers: CNS involvement, Heart failure, 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: 3

Duration: 42 months

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, palbociclib and ibrutinib, for patients with mantle cell lymphoma who have previously received treatment. Palbociclib stops cancer cells from dividing, while ibrutinib blocks signals that help cancer cells grow. The goal is to see how well this combination works in slowing down or stopping the cancer.

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

The trial does not specify if you must stop all current medications, but you cannot take strong or moderate inhibitors or strong inducers of CYP3A isoenzymes within 7 days of starting the study treatment. You may continue taking prednisone at a maximum dose of 20 mg daily for symptom control.

What data supports the effectiveness of the drugs Palbociclib and Ibrutinib for treating Mantle Cell Lymphoma?

A phase 1 trial showed that combining palbociclib with ibrutinib in patients with previously treated mantle cell lymphoma resulted in a 67% overall response rate and a 37% complete response rate, with a 2-year progression-free survival of 59.4%. ^{1 2 3 4 5}

Is the combination of Palbociclib and Ibrutinib safe for humans?

In a phase 1 trial for mantle cell lymphoma, the combination of Palbociclib and Ibrutinib was generally safe, but some patients experienced serious side effects like severe rash, low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), high blood pressure (hypertension), fever with low white blood cells (febrile neutropenia), and lung infections. ^{1 2 4 6 7}

How is the drug combination of Palbociclib and Ibrutinib unique for treating mantle cell lymphoma?

The combination of Palbociclib and Ibrutinib is unique because it targets mantle cell lymphoma by using Palbociclib to overcome resistance to Ibrutinib, which is a common issue with this type of cancer. This approach aims to improve treatment outcomes by combining the effects of a CDK4/6 inhibitor (Palbociclib) with a Bruton's tyrosine kinase inhibitor (Ibrutinib). ^{1 2 4 8 9}

Research Team

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Kami Maddocks, MD

Principal Investigator

Ohio State University

Eligibility Criteria

Adults with previously treated mantle cell lymphoma who have had at least one prior systemic therapy can join. They must be able to take oral medication, not have severe heart conditions or active infections, and agree to use effective contraception. Those with certain other cancers, recent heart attacks, or uncontrolled illnesses cannot participate.

Inclusion Criteria

I have a tumor that is visible on scans or specific blood cell counts indicating cancer.

I have undergone at least one treatment that affects my whole body.

Subjects must be able to provide written, informed consent

Exclusion Criteria

History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.

I have never taken CDK4/6 inhibitors for my condition.

I have not taken any BTK inhibitor medication in the last 90 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive palbociclib and ibrutinib. Palbociclib is administered at 100 mg oral once daily for 21 days on followed by 7 days off, and ibrutinib is administered at 560 mg oral continuously.

42 months

PET/CT and/or CT every 3 cycles for the first year, then every 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ibrutinib
• Palbociclib

Trial Overview The trial is testing the combination of two drugs: Palbociclib and Ibrutinib in patients with mantle cell lymphoma that has been treated before. It's a phase II study where everyone gets both drugs for cycles of 28 days to see how well they work together.

Participant Groups

Group I: Single Arm Experimental Treatment 2 Interventions

All patients will receive palbociclib at 100 mg oral once a day for 21 days, followed by 7 days off. Ibrutinib will be administered at 560 mg oral continuously.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a phase 2 trial involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib, lenalidomide, and rituximab resulted in a high overall response rate of 76%, with 56% achieving a complete response, suggesting this triplet therapy is effective.

While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment-related deaths, highlighting the need for careful monitoring and further evaluation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Jerkeman, M., Eskelund, CW., Hutchings, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma. [2021]

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

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib approved for mantle cell lymphoma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Postibrutinib outcomes in patients with mantle cell lymphoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib in patients with relapsed/refractory mantle cell lymphoma: a real-life, retrospective, multicenter trial on behalf of the "RTL" (regional Tuscan lymphoma network). [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

[scRNA-sequencing uncovers metabolism and CD52 as new targets in ibrutinib-surviving mantle cell lymphoma cells]. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma. [2023]