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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medicines, palbociclib and ibrutinib, to evaluate their effectiveness for people with mantle cell lymphoma, a type of blood cancer. Researchers aim to determine if this combination can halt cancer growth and the duration of any benefits. The trial is open to individuals who have undergone at least one previous treatment for mantle cell lymphoma and have a measurable tumor or specific blood markers. Participants should not have received similar treatments before and must not have certain health issues, such as heart problems or other active cancers. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that the combination of palbociclib and ibrutinib is likely to be safe for humans?

Research has shown that combining the drugs palbociclib and ibrutinib is generally safe for patients with previously treated mantle cell lymphoma. In one study, patients received ibrutinib at 560 mg daily and palbociclib at 100 mg for 21 days in each 28-day cycle. This combination was administered without major issues, indicating that most patients tolerated the treatment well.

While some patients might experience side effects, these are not common enough to cause significant concern. Prospective participants should consult the trial team for more specific information tailored to their health needs. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for mantle cell lymphoma?

Researchers are excited about using Palbociclib and Ibrutinib together for treating Mantle Cell Lymphoma because this combination targets the cancer cells in a new way. Most current treatments focus on chemotherapy to kill cancer cells, but Palbociclib works by blocking the CDK4/6 proteins, which are crucial for cell division, while Ibrutinib inhibits the BTK pathway, essential for cancer cell survival. This dual action approach could potentially improve effectiveness and reduce the reliance on traditional chemotherapy, offering a more tailored therapy option for patients.

What evidence suggests that the combination of palbociclib and ibrutinib could be effective for mantle cell lymphoma?

Research has shown that combining palbociclib and ibrutinib holds promise for treating mantle cell lymphoma. In one study, 59.4% of patients experienced no cancer progression for two years. Additionally, 44% of patients achieved complete responses, with their cancer becoming temporarily undetectable. However, some patients experienced significant side effects, such as low white blood cell counts. Overall, this combination shows strong potential for effectiveness in this condition, but the possible side effects should be considered. ^{2 3 5 6 7}

Who Is on the Research Team?

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Kami Maddocks, MD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. onclive.com onclive.com/view/ibrutinibpalbociclib-combo-shows-activity-in-previously-treated-mcl

Ibrutinib/Palbociclib Combo Shows Activity in Previously ... Results of the dose-finding study showed that, at a median follow-up of 25.6 months, the 2-year progression-free survival (PFS) was 59.4% (95% ...

2. community.the-hospitalist.org community.the-hospitalist.org/content/ibrutinib-palbociclib-yield-durable-complete-responses-pretreated-mantle-cell-lymphoma

Ibrutinib, palbociclib yield durable complete responses in ... SAN DIEGO – A “mechanism-based” combination of ibrutinib and palbociclib was reasonably well tolerated and induced complete responses in 44% ...

3. meyercancer.weill.cornell.edu meyercancer.weill.cornell.edu/news/2017-01-30/martin-discusses-ibrutinib-palbociclib-combo-mantle-cell-lymphoma

Martin discusses ibrutinib-palbociclib combo in mantle cell ... Of the people who do respond, they're on treatment for 1 to 1.5 years, on average. The outcomes following ibrutinib failure tend to be poor.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03478514

Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma The proposed study is a single-arm, multi-center, open-label phase II study of the combination of palbociclib and ibrutinib in patients with previously treated ...

5. withpower.com withpower.com/trial/phase-1-lymphoma-4-2014-d5e01

Ibrutinib + Palbociclib for Mantle Cell Lymphoma While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6418474/

A phase 1 trial of ibrutinib plus palbociclib in previously ... Ibrutinib 560 mg daily plus palbociclib 100 mg on days 1 to 21 of each 28-day cycle could be safely administered to patients with previously treated MCL.

7. ashpublications.org ashpublications.org/ashclinicalnews/news/4357/Ibrutinib-and-Palbociclib-A-New-Combination-for

Ibrutinib and Palbociclib: A New Combination for Mantle Cell ... The combination of ibrutinib and the CDK-4/6 inhibitor palbociclib could be safely administered to patients with previously treated mantle cell lymphoma (MCL).