Palbociclib in Combination With Lenalidomide and Dexamethasone for Multiple Myeloma

Inclusion Criteria: * Subject must voluntarily sign and understand written informed consent. * Subject is ≥18 years at the time of signing the consent form. * Subject has histologically confirmed multiple myeloma that expresses phosphorylated retinoblastoma protein (pRb), as assessed using a historical biopsy sample if available, or a freshly obtained tumor sample. * Subject has relapsed or refractory myeloma as defined by progression of disease either after prior therapy or lack of response to currently used therapy. * Subject must have received and relapsed or progressed after prior treatment with bortezomib. * Subject has measurable disease as defined by \> 0.5 g/dL serum monoclonal protein, \>10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI. * Subject has a Karnofsky performance status ≥60% (\>50% if due to bony involvement of myeloma * Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin). * Subject is registered into the mandatory Revlimid REMS®program, and is willing and able to comply with the requirements of Revlimid REMS® program. * If subject is a female of childbearing potential (FCBP), she must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. Men must agree to continue birth control for 90 days post-last dose of PD-0332991 * All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program. * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. * Subject has a life expectancy ≥ 3 months * Subjects must meet the following laboratory parameters: * Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) * Platelet count ≥ 75,000/mm3 (75 x 109/L) * Serum SGOT/AST \<3.0 x upper limits of normal (ULN) * Serum SGPT/ALT \<3.0 x upper limits of normal (ULN) * Serum creatinine clearance, (either calculated or directly measured). ≥ 60cc/min * Serum total bilirubin \<2.0 mg/dL (34 μmol/L) Exclusion Criteria: * Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning). * Subject has a prior history of other malignancies unless disease free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score \< 7 with stable prostate specific antigen (PSA) levels. * Subject has had myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction \< 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Female subject who is pregnant or lactating. * Subject has known HIV infection * Subject has known active hepatitis B or hepatitis C infection. * Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program. * Subject has known hypersensitivity to dexamethasone or lenalidomide. * Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment. * Subject has any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent. * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.