Pomalidomide for Chronic Graft-versus-Host Disease
Condition: Graft vs Host Disease; Graft-Versus-Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Pomalidomide
Intervention description: 0.5 mg/day with and/or without Dose Escalation and 0.5 mg/day- 2.0 mg/day by mouth (PO) QD(every day) of each 28 day cycle
Intervention MeSH terms: Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Immune Modulatory; Systemic Absorption; Oral Agent

Summary:

      Background:

      - Pomalidomide is a drug that alters the body's immune response. It may help people who have
      chronic graft-versus-host disease (GvHD). GvHD may appear after a stem cell transplant, when
      immune cells in the transplant try to attack tissues in the person who received the
      transplant. GvHD is not easy to treat, and often does not respond to standard treatments.
      Researchers want to see if pomalidomide is a safe and effective treatment for GvHD.

      Objectives:

      - To test the safety and effectiveness of pomalidomide for GvHD that has not responded to
      standard treatments.

      Eligibility:

      - Individuals at least 18 years of age who have GvHD that has not responded to standard
      treatments.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will also be collected. A lung function test and imaging studies will also be
           given.

        -  Participants will take pomalidomide capsules once a day for 4-week periods called
           cycles.

        -  Treatment will be monitored with frequent blood tests and imaging studies. Saliva
           samples and skin and mouth tissue biopsies will also be collected during treatment.

        -  Treatment will continue for six cycles (6 months), unless the GvHD gets worse or side
           effects are too severe. If the GvHD has improved at the end of the six cycles,
           participants may be able to continue to take pomalidomide for up to six more cycles.
    

Eligibility criteria:

        -  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.