A Randomized Phase 2 Single-Center Study of Pomalidomide for Chronic GvHD

Date de début de l'étude : 30 août 2012

INCLUSION CRITERIA Moderate or severe chronic graft-versus-host disease (cGvHD) diagnosed and staged per National Institutes of Health (NIH) criteria Greater than or equal to18-75 years of age, because no dosing or adverse event data are currently available on the use of pomalidomide in persons greater than or equal to18 years of age Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d prednisone for >8 weeks) or second-line systemic therapy If taking systemic therapy for cGvHD at the time of enrollment, must be on a stable or tapering schedule in the preceding 4 weeks (extracorporeal photopheresis has to be stopped at least by 4 weeks before enrollment) Karnofsky performance score greater than or equal to 60% Life expectancy >3 months Stable primary malignancy for previous 3 months Agree to adhere to methods of contraception and other fertility control measures as prescribed by the protocol Because agents of this class are known to be teratogenic, women of childbearing potential and men must agree to use effective forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Females of childbearing potential (FCBP) (Cross) 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 starting pomalidomide 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 pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND Education and Counseling Guidance Document. Male Subjects Must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation of study drug even if he has undergone a successful vasectomy Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation of study drug. Must agree that if a pregnancy or a positive pregnancy test does occur in a study subject or the partner of a male study subject during study participation, study drug must be immediately discontinued. Patients must agree to not share study drug with anyone during participation in the study. Ability of subject to understand and the willingness to sign a written informed consent document. All study participants must be registered into the mandatory POMALYST REMS (TM) program, and be willing and able to comply with the requirements of the POMALYST REMS (TM) program. EXCLUSION CRITERIA: Acute GvHD, classic (less than or equal to day 100) or late-onset (>day 100) Systemic immune suppression or systemic therapy for cGvHD started within preceding 4 weeks including extracorporeal photopheresis Hypersensitivity to thalidomide, lenalidomide or pomalidomide Any serious medical condition which places the subject at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study, including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Neutrophil <1.0x10(9)/L, platelets <75x10(9)/L, estimated creatinine clearance <50 mL/min/1.73m(2) (Cockroft-Gault formula) total bilirubin >3 mg/dL, transaminase>3xUNL Uncontrolled infection Active human immunodeficiency virus 1 (HIV-1), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection Uncontrolled arrhythmias or symptomatic heart disease or left ventricular ejection fraction (LVEF) <45% Other cancer except that for which the transplant was done <2 years before study entry, except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or breast Taking other investigational drugs NIH lung score 3 Pregnant women are excluded from this study because pomalidomide has potential for teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pomalidomide, breastfeeding must be discontinued while the mother is taking study drug and for at least 28 days after discontinuation of study drug. These potential risks may also apply to other agents used in this study.