Ibrutinib + Palbociclib for Mantle Cell Lymphoma

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: BTK inhibitors, CDK4/6 inhibitors

Disqualifiers: CNS involvement, Hepatitis B/C, Uncontrolled HIV, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and examine the side effects of combining ibrutinib (Imbruvica) and palbociclib (Ibrance) for treating previously treated mantle cell lymphoma. These drugs block enzymes essential for cancer cell growth, and palbociclib may enhance ibrutinib's effect. Ideal participants have been diagnosed with mantle cell lymphoma, have visible tumors or a specific blood condition, and have undergone prior treatments, excluding certain ones like BTK inhibitors or CDK4/6 inhibitors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that ibrutinib and palbociclib are likely to be safe for humans?

Research shows that patients with mantle cell lymphoma who have already received treatment can safely take a combination of ibrutinib and palbociclib. Earlier studies found this combination to be generally well-tolerated. Patients took ibrutinib daily and palbociclib for 21 days in a 28-day cycle. Although some patients experienced side effects, these were manageable and did not interrupt the treatment. This suggests that the treatment is generally safe when administered as directed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ibrutinib and Palbociclib for treating Mantle Cell Lymphoma because of their unique mechanisms of action. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, which blocks signals that help cancer cells survive and grow. Meanwhile, Palbociclib is a CDK4/6 inhibitor, preventing cancer cells from dividing and multiplying. Together, these drugs target different pathways that cancer cells use, potentially making the treatment more effective than current standard options, which typically involve chemotherapy and single-agent targeted therapies.

What evidence suggests that ibrutinib and palbociclib might be an effective treatment for mantle cell lymphoma?

Research has shown that the combination of ibrutinib and palbociclib, which participants in this trial will receive, holds promise for treating mantle cell lymphoma (MCL). Studies have found that this drug combination is effective in 67% of patients with MCL. Over a 2-year period, about 59.4% of patients did not experience disease progression. Patients who respond to the treatment typically continue it for about 1 to 1.5 years. Ibrutinib blocks certain enzymes that cancer cells need to grow, while palbociclib may enhance its effects by making cancer cells more sensitive to the treatment. ^{1 2 5 6 7}

Who Is on the Research Team?

Peter Martin

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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.

I am willing to have biopsies before and if my cancer progresses.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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. 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 ...

2. aacrjournals.org aacrjournals.org/cancerdiscovery/article-pdf/9/3/318/2942780/318.pdf

Ibrutinib plus Palbociclib Has Efficacy in Mantle Cell Lymphoma Major finding:The BTK inhibitor ibrutinib plus the CDK4 inhibitor palbociclib achieves responses in 67% of patients with MCL. Clinical relevance: Responses to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4556969/

Ibrutinib in mantle cell lymphoma patients: glass half full? ... Ibrutinib is a very promising agent for patients with MCL with notable response rates. However, when used as a single agent, around one third of patients ...

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

A phase 1 trial of ibrutinib plus palbociclib in previously ... With a median follow-up in survivors of 25.6 months, the 2-year PFS was 59.4% (95% confidence interval, 37.9%-80.9%), and the 2-year overall survival was 60.6% ...

5. 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.

6. 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).

7. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)00237-3/fulltext

Treatment Landscape of Relapsed/Refractory Mantle Cell ... In this report, we provide an updated literature review that covers recent clinical data about the safety and efficacy of novel therapies for the management of ...