Ibrutinib + Palbociclib for Mantle Cell Lymphoma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of ibrutinib and palbociclib in treating patients with previously treated mantle cell lymphoma. Ibrutinib and palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Palbociclib may also help ibrutinib work better by making cancer cells more sensitive to the drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on certain medications like strong CYP3A inhibitors or systemic immunosuppressants. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Ibrutinib and Palbociclib for treating mantle cell lymphoma?

Research shows that Ibrutinib is effective for mantle cell lymphoma, with FDA approval for patients who have had prior treatment. A phase 1 trial combining Ibrutinib and Palbociclib showed promising results, with 67% of patients responding to the treatment and a 2-year progression-free survival rate of 59.4%. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Palbociclib safe for treating mantle cell lymphoma?

In a phase 1 trial, the combination of Ibrutinib and Palbociclib for mantle cell lymphoma showed some serious side effects, including a rash, low white blood cell count (neutropenia), low platelet count (thrombocytopenia), high blood pressure (hypertension), fever with low white blood cell count (febrile neutropenia), and lung infections. Ibrutinib alone has been generally well-tolerated in other studies, but it can cause diarrhea, serious infections, bleeding issues, and heart problems like irregular heartbeat. ^{2 3 6 7 8}

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

The combination of Ibrutinib and Palbociclib is unique because it targets mantle cell lymphoma by using Ibrutinib to inhibit Bruton's tyrosine kinase and Palbociclib to block CDK4/6, which helps overcome resistance to Ibrutinib alone. This approach aims to improve treatment outcomes for patients who have previously been treated for this condition. ^{1 2 3 4 9}

Research Team

Peter Martin

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

Adults with previously treated mantle cell lymphoma, confirmed by specific tests, who have measurable disease and normal organ/marrow function. They must not have had certain treatments recently and should agree to use contraception. Excluded are those with active hepatitis B/C, uncontrolled illnesses, recent major surgery or live vaccines, strong CYP3A inhibitor use within 7 days prior to the trial, or a history of stroke/heart issues within the past 6 months.

Inclusion Criteria

Your white blood cell count is normal and is at least 750 cells per microliter within the past 2 weeks before joining the study.

My liver is not severely damaged according to the NCI/Child Pugh classification.

I am not on more than 20 mg of corticosteroids daily or can reduce it below that 7 days before starting the trial.

Exclusion Criteria

I haven't had a severe heart issue or uncontrolled heart condition in the last 6 months.

I am not pregnant or breastfeeding.

My cancer has not spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily on days 1-28 and palbociclib orally once daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Treatment Details

Interventions

• Ibrutinib
• Palbociclib

Trial Overview The trial is testing the combination of two drugs: Ibrutinib and Palbociclib for treating mantle cell lymphoma that has been treated before. It aims to find out the best dose and side effects by seeing how these drugs can block enzymes needed for cancer cells' growth and make them more sensitive to treatment.

Participant Groups

Group I: Treatment (ibrutinib, palbociclib) Experimental Treatment 4 Interventions

Patients receive ibrutinib PO QD on days 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II study involving 50 previously untreated patients with indolent mantle cell lymphoma (MCL), the combination of ibrutinib and rituximab resulted in an impressive 80% complete response rate after 12 treatment cycles.

The treatment also led to undetectable minimal residual disease (MRD) in 87% of patients, allowing 69% of evaluable patients to safely discontinue ibrutinib after 2 years, although caution is advised for those with TP53 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Giné, E., de la Cruz, F., Jiménez Ubieto, A., et al.[2022]

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]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

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

Ibrutinib approved for mantle cell lymphoma. [2021]

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

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

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

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. [2022]

5. 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]

6. France pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. [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. France pubmed.ncbi.nlm.nih.gov

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

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