A Phase II Study of Palbociclib (PD-0332991) in Combination With Ibrutinib in Patients With Previously Treated Mantle Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Palbociclib
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Alliance Foundation Trials, LLC.
- Enrollment
- 39
- Locations
- 18
- Primary Endpoint
- Progression free survival
- Status
- Active, Not Recruiting
- Last Updated
- 23 days ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 D
- •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.
- •Subjects must have received at least one prior systemic therapy.
- •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.
- •Subjects must be age ≥ 18 years
- •ECOG performance status ≤ 2
- •Patients must have normal organ and marrow function as defined below:
- •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;
Exclusion Criteria
- •Subjects that have received prior CDK4/6 inhibitor will not be eligible.
- •Subjects that have received any prior BTK inhibitor \> 90 days prior to enrollment will not be eligible.
- •Subjects with known or suspected CNS involvement.
- •Concurrent therapy with other investigational products.
- •History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
- •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).
- •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.
- •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.
- •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.
- •Subjects must agree to use barrier contraceptive methods throughout the study period up until at least 90 days post last palbociclib dose.
Arms & Interventions
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.
Intervention: Palbociclib
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.
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Progression free survival
Time Frame: 42 months
Time interval between registration and progression or death
Secondary Outcomes
- Overall survival(42 months)
- Duration of response(42 months)
- Overall Response Rate(42 Months)
- Complete Response(42 Months)
- Toxicity: Incidence and severity of adverse events by summaries of toxicity data/contingency tables(42 Months)