Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma

February 29, 2024 updated by: Alliance Foundation Trials, LLC.

A Phase II Study of Palbociclib (PD-0332991) in Combination With Ibrutinib in Patients With Previously Treated 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 mantle cell lymphoma to evaluate the efficacy of this combination, with the primary objective of the study being to assess median PFS and the secondary objectives to include ORR, CR, DOR, OS and toxicity. Subjects will be enrolled and treated with palbociclib and ibrutinib with each cycle of therapy being 28 days. Treatment will be based on the recommended phase II dose (RP2D) from the phase I combination trial.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Treatment will consist of:

  • Palbociclib administered at 100 mg oral once daily for 21 days on followed by 7 days off
  • Ibrutinib administered at 560 mg oral continuously

Patients will continue to receive study drugs until disease progression, unacceptable toxicity, or withdrawal of consent. If at any time one of the agents is held due to toxicity, the other agent may be continued in those patients who are receiving clinical benefit.

Response will be assessed by PET/CT and/or CT every 3 cycles while on therapy for the first year and then every 6 cycles thereafter until disease progression or at the investigator's discretion if otherwise medically indicated. A PET will be required to confirm CR. A bone marrow biopsy will be performed in patients with bone marrow involvement at the start of therapy to confirm complete response once patients have otherwise met criteria for CR.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Greenebaum Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ypsilanti, Michigan, United States, 48197
        • St. Joseph Mercy Hospital Cancer Care Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina - Hollings Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects must have histologically or cytologically confirmed MCL as defined by the World Health Organization. All patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry (IHC) for cyclin D1.
  2. Subjects must have measurable disease defined as at least one tumor lesion of at least 1.5 cm by CT or MRI, PET positive lesion(s) or a peripheral blood CD5+, CD19+ lymphocyte count of at least 5,000 cells/µL.
  3. Subjects must have received at least one prior systemic therapy.
  4. Subjects who have received prior autologous stem cell transplant are eligible. Patients that have undergone prior allogeneic stem cell transplant will only be eligible if the patient is no longer taking immunosuppressive therapy and there are no significant ongoing transplant-related adverse effects.
  5. Subjects must be age ≥ 18 years
  6. ECOG performance status ≤ 2
  7. Patients must have normal organ and marrow function as defined below:

  8. Laboratory Values:

    • ANC ≥ 1000 cells/μL, unless bone marrow involvement in MCL, then ANC >500 cells/μL;
    • Platelets ≥ 75,000 cells/μL, unless bone marrow involvement in MCL, then platelets >30,000 cells/μL;
    • Calculated creatinine clearance ≥30mL/min;
    • AST or ALT ≤ 2.5x ULN;
    • Total bilirubin ≤ 1.5x ULN;
    • QTc ≤ 480 ms
  9. Subjects must be able to provide written, informed consent
  10. Subjects must have recovered from adverse events to ≤ grade 1 from prior therapies
  11. Subjects must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption
  12. Subjects may be receiving prednisone at a maximum dose of 20 mg orally daily for symptom control.

  13. Serum or urine pregnancy test must be negative within 7 days of starting study treatment in women of childbearing potential. Women of childbearing potential and men with female partners who are able to become pregnant are required to use a highly effective form of barrier contraception for the duration of the study and for 90 days after the last dose of study drug. Adequate contraception is defined as abstinence or two forms non hormonal contraception, which is a combination of two forms of the following:

    • Condom with spermicidal foam/gel/cream/suppository
    • occlusive cap (diaphragm or cervical vault caps) with spermicidal
    • non hormonal intrauterine device (IVD)
  14. No evidence of active hepatitis B or C infections (i.e., no positive serology for anti-HBc or anti-HCV antibodies)
  15. HBV seropositive patients (HBsAg +) are eligible if they are closely monitored for evidence of active HBV infection by HBV DNA testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose.

  16. Patients with HIV infection are eligible, provided they meet the following:

    • No evidence of coinfection with hepatitis B or C
    • CD4+ cell count ≥ 400/mm3
    • No evidence of resistant strains of HIV
    • If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
    • No history of AIDS-defining conditions
    • No use of strong CYP3A4/5 inhibitors or inducers

Exclusion Criteria:

  1. Subjects that have received prior CDK4/6 inhibitor will not be eligible.
  2. Subjects that have received any prior BTK inhibitor > 90 days prior to enrollment will not be eligible.
  3. Subjects with known or suspected CNS involvement.
  4. Concurrent therapy with other investigational products.
  5. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
  6. Subjects receiving any medications or substances that are strong or moderate inhibitors or strong inducers of CYP3A isoenzymes within 7 days of starting study treatment (See Appendix II).
  7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
  8. Subjects with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
  9. Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to registration, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding should be discontinued prior to study entry.
  10. Subjects must agree to use barrier contraceptive methods throughout the study period up until at least 90 days post last palbociclib dose.
  11. Subjects with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.
  12. Subjects with another active malignancy that limits survival.
  13. Subjects with a bleeding diathesis are not eligible.
  14. Subjects with transfusion-dependent thrombocytopenia are not eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm

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.
Drug: Palbociclib
Taken at 100 mg once daily for 21 days, followed by 7 days off
Other Names:
  • Ibrance; PD-0332991
Drug: Ibrutinib
560 mg taken orally all patients throughout the study
Other Names:
  • Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 42 months
Time interval between registration and progression or death
42 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 42 months
time from registration to death due to any cause
42 months
Duration of response
Time Frame: 42 months
Time from documentation of tumor response to disease progression
42 months
Overall Response Rate
Time Frame: 42 Months
Proportion of patients with reduction in tumor burden of a predefined amount
42 Months
Complete Response
Time Frame: 42 Months
Disappearance of all non-target lesions and normalization of tumor marker level
42 Months
Toxicity: Incidence and severity of adverse events by summaries of toxicity data/contingency tables
Time Frame: 42 Months
Evaluation of incidence and severity of adverse events by summaries of toxicity data/contingency tables
42 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance Foundation Trials, LLC.

Collaborators

Pfizer

Investigators

  • Study Chair: Kami Maddocks, MD, Ohio State University
  • Principal Investigator: Evanthia Galanis, MD, Alliance Foundation Trials, LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2018

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

March 21, 2018

First Submitted That Met QC Criteria

March 26, 2018

First Posted (Actual)

March 27, 2018

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFT-32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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