Details

Details

Title A Phase I single arm study to assess the safety and efficacy of Pomalidomide in patients with bleeding due to Hereditary Hemorrhagic Telangiectasia and Refractory Angiodysplasia

IRB CASE4Z14

CC 14-786

Hospital Main Campus

Phase Phase 1

Disease Telangiectasia, Vascular Ectasia

Drug Pomalidomide

Description

Description

Primary Objective:
  • To compare the requirement for transfusion and intravenous iron administration in individual patients with HHT related GI bleeding or vascular ectasia, or with HHT-related epistaxis, in the 4 month period before initiation of pomalidomide with that over a 4 month period following pomalidomide therapy.
Secondary Objectives:
  1. To determine the percentage of patients who meet the primary objective who maintain their response for at least 6 months after discontinuation of pomalidomide.
  2. To compare the responses to pomalidomide in patients with and without genetically-confirmed HHT.
  3. To determine whether mutations in the Endoglin (Eng),activin-like kinase 1 (Alk-1) and Smad-4 genes are present in patients with angiodysplasia who have not previously undergone genetic testing
  4. To analyze patient plasma, cellular and subcellular fractions for biomarkers correlating with a response to pomalidomide.
  5. To initiate a biorepository of plasma samples from patients with gastrointestinal bleeding due to vascular ectasia with or without HHT who have been treated with Pomalidomide
  6. To determine the effect of Pomalidomide treatment on the epistaxis severity score.
Inclusion Criteria

Inclusion Criteria

  1. Age > 18 years
  2. For patients with GI bleeding, transfusion of at least 4 units of blood and/or four doses of intravenous iron over the preceding four months.
  3. Platelet count ≥ 100,000/μl
  4. WBC ≥ 4,000/μl with ANC > 1,200/μl
  5. INR ≤ 1.3 and normal activated partial thromboplastin time (aPTT)
  6. For patients with GI bleeding, endoscopically-documented angiodysplasia and/or arteriovenous malformations at some point during prior medical evaluation or therapy.
  7. Females of childbearing potential (FCBP) 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 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.
  8. Ability to understand and sign informed consent
  9. All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program
  10. For patients with epistaxis, an epistaxis severity score between 4 and 7
  11. For patients with epistaxis, a requirement for 2 units transfusion or 500 mg of iron in the preceding four months.
Exclusion Criteria

Exclusion Criteria

  1. Pregnancy (must be excluded by two urine or serum tests for β-HCG in all women of child-bearing potential). Pregnancy testing must follow pregnancy testing requirements as outlined in the POMALYST REMS™ program.
  2. Breast feeding
  3. Renal insufficiency, serum creatinine > 2.0 mg/dl
  4. Hepatic insufficiency, bilirubin > 2.0 or transaminases > 3.0 x normal
  5. Prior treatment with Thalidomide or other imid drugs within previous 12 months
  6. Prior treatment with Avastin (systemic or nasal) within previous 6 weeks
  7. History of prior thromboembolism with known thrombophilia
  8. Peripheral neuropathy, as determined from neurologic consultation
  9. Underlying hypoproliferative anemia (i.e. myelodysplasia)
  10. Inherited or significant acquired coagulopathy (i.e. hemophilia, advanced liver disease)
  11. Chronic aspirin, NSAID therapy or anticoagulation therapy
  12. Currently enrolled in other interventional trials
  13. Known hypersensitivity to thalidomide or lenalidomide.
  14. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, or similar drugs.
  15. Anything that in the investigator's opinion is likely to interfere with completion of the study