Phase II Palbociclib +Ibrutinib in Mantle Cell Lymphoma

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.
• •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)
• •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