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Trial record 1 of 1 for:    NCT03478514
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Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03478514
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : May 12, 2020
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Tracking Information
First Submitted Date  ICMJE March 21, 2018
First Posted Date  ICMJE March 27, 2018
Last Update Posted Date May 12, 2020
Actual Study Start Date  ICMJE September 11, 2018
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2018)
Progression free survival [ Time Frame: 42 months ]
Time interval between registration and progression or death
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2018)
  • Overall survival [ Time Frame: 42 months ]
    time from registration to death due to any cause
  • Duration of response [ Time Frame: 42 months ]
    Time from documentation of tumor response to disease progression
  • Overall Response Rate [ Time Frame: 42 Months ]
    Proportion of patients with reduction in tumor burden of a predefined amount
  • Complete Response [ Time Frame: 42 Months ]
    Disappearance of all non-target lesions and normalization of tumor marker level
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma
Official Title  ICMJE A Phase II Study of Palbociclib (PD-0332991) in Combination With Ibrutinib in Patients With Previously Treated Mantle Cell Lymphoma
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Mantle Cell Lymphoma
  • B Cell Lymphoma
Intervention  ICMJE
  • Drug: Palbociclib
    Taken at 100 mg once daily for 21 days, followed by 7 days off
    Other Name: Ibrance; PD-0332991
  • Drug: Ibrutinib
    560 mg taken orally all patients throughout the study
    Other Name: Imbruvica
Study Arms  ICMJE 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
  • Drug: Ibrutinib
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 26, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Subjects that have received either prior BTK inhibitor or CDK4/6 inhibitor will not be eligible
  8. Patients must have normal organ and marrow function as defined below:
  9. Laboratory Values:

    • ANC ≥ 1000 cells/μL;
    • Platelets ≥ 75,000 cells/μL;
    • Calculated creatinine clearance ≥30mL/min;
    • AST or ALT ≤ 2.5x ULN;
    • Total bilirubin ≤ 1.5x ULN;
    • QTc ≤ 480 ms
  10. Subjects must be able to provide written, informed consent
  11. Subjects must have recovered from adverse events to ≤ grade 1 from prior therapies
  12. Subjects must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption
  13. Subjects may be receiving prednisone at a maximum dose of 20 mg orally daily for symptom control.
  14. 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)
  15. No evidence of active hepatitis B or C infections (i.e., no positive serology for anti-HBc or anti-HCV antibodies)
  16. 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.
  17. 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 with known or suspected CNS involvement
  2. Concurrent therapy with other investigational products
  3. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib
  4. 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)
  5. 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.
  6. 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.
  7. 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.
  8. Subjects must agree to use barrier contraceptive methods throughout the study period up until at least 90 days post last palbociclib dose.
  9. Subjects with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.
  10. Subjects with another active malignancy that limits survival
  11. Subjects with a bleeding diathesis are not eligible.
  12. Subjects with transfusion-dependent thrombocytopenia are not eligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joseph B. Gannon Jr. 617-525-8177
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03478514
Other Study ID Numbers  ICMJE AFT-32
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Alliance Foundation Trials, LLC.
Study Sponsor  ICMJE Alliance Foundation Trials, LLC.
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Monica Bertagnolli, MD Alliance Foundation Trials, LLC.
Study Chair: Kami Maddocks, MD Ohio State University
PRS Account Alliance Foundation Trials, LLC.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP