Pomalidomide for Chronic Graft-versus-Host Disease
Condition: Graft vs Host Disease; Graft-Versus-Host Disease
MeSH terms: Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      BACKGROUND:

        -  Chronic graft-versus-host disease (cGvHD) is the leading cause of non-relapse morbidity
           and mortality in persons after allogeneic hematopoietic cell transplants.

        -  About 50% of persons with cGvHD have disease refractory to systemic corticosteroids and
           there is no standard second-line therapy.

        -  Thalidomide, a drug with immune-modulating effects, was active in advanced cGvHD but was
           difficult to use at appropriate doses.

        -  Pomalidomide is related to thalidomide but with higher potency and more favorable
           toxicity profile. It is active in multiple myeloma and myeloproliferative neoplasm
           associated myelofibrosis. Preliminary data in humans with cGvHD are encouraging but data
           are limited.

      OBJECTIVES:

      - Primary: Determine whether pomalidomide is effective in persons with moderate or severe
      cGvHD not controlled by corticosteroids.

      ELIGIBILITY:

      Inclusion Criteria

        -  Moderate or severe cGvHD per National Institutes of Health (NIH) criteria

        -  Age 18 to 75 years old

        -  Karnofsky performance score greater than or equal to 60%

        -  Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d
           prednisone for greater than or equal to 8 weeks) or second-line therapy

        -  Receiving stable or tapering doses of systemic therapy in the preceding 4 weeks

        -  Agree to adhere to methods of contraception and other fertility control measures as
           prescribed by the protocol

      Exclusion Criteria

        -  Acute GvHD (classic and late per NIH criteria)

        -  Absolute neutrophils <1.0x10(9)/L, platelets <75x10(9)/L, estimated creatinine clearance
           <50 mL/min/1.73m(2)

        -  NIH lung score 3

        -  Pregnant or lactating

        -  Uncontrolled infection

      DESIGN:

      Randomized phase 2 trial with the single stage selection design. Patients will receive either
      a constant low dose of pomalidomide (0.5 mg/day) for six months or a strategy of increasing
      dose of pomalidomide from 0.5 mg/d up through each individual patient's maximum tolerated
      dose, with escalations by 0.5 mg/d every 2 weeks to a maximum of 2.0 mg/d. As an early
      stopping rule for futility, if after 7 patients have enrolled on either arm, 0 have
      responded, then no further patients will be accrued to that arm as soon as this can be
      determined. To protect patient safety, an early stopping rule will be implemented. With two
      arms, each of which has a maximal accrual of 16 patients, up to 32 evaluable patients will be
      randomized. Response assessments will occur every 3 months with primary efficacy endpoint
      evaluated at 6 months. Patients with responding disease will continue therapy for another 6
      months.
    

Intervention name(s): Pomalidomide
Intervention type(s): Drug
Intervention description(s): 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
Other intervention name(s): POMALYST
Intervention MeSH terms: Pomalidomide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immune Modulatory; Systemic Absorption; Oral Agent