Pomalidomide for the Treatment of Bleeding in HHT

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase II placebo-controlled double-blind study of pomalidomide in patients with hereditary hemorrhagic telangiectasia (HHT) with moderate to severe epistaxis who require parenteral iron infusions or blood transfusions. A total of 159 patients will be randomized 2:1 to treatment with oral pomalidomide or matching placebo for 24 weeks. Mean change from baseline to 24 weeks in the Epistaxis Severity Score (ESS) will be compared between treatment groups to determine pomalidomide efficacy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Cleveland Clinic
• Collaborator: RTI International
• Treatments: Pomalidomide; Thalidomide

Criteria

Inclusion Criteria:

1. A clinical diagnosis of HHT as defined by the Curacao criteria

2. Age > 18 years

3. Platelet count ≥ 100,000/µl

4. WBC ≥ 2,500/µl

5. INR ≤ 1.4 and normal ± 2 sec activated partial thromboplastin time (aPTT) by local laboratory criteria (except for patients on a stable dose of warfarin or direct oral anticoagulants)

6. Epistaxis severity score ≥ 3 measured over the preceding three months, measured at the screening visit

7. A requirement for anemia, as determined by local laboratory normal ranges, and/or parenteral infusion of at least 250 mg of iron or transfusion of 1 unit of blood over the 24 weeks preceding the screening visit

8. Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing (once very two weeks) as required in the POMALYST REMS program. FCBP must a negative serum pregnancy test with a sensitivity of at least 50 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. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy.

9. Ability to understand and sign informed consent

10. All study participants must agree to be registered into the FDA mandated POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program

Exclusion Criteria:

1. Women currently breast feeding

2. Renal insufficiency, serum creatinine > 2.0 mg/dl

3. Hepatic insufficiency, bilirubin > 2.0 (or >4.0 in the setting of a prior clinical or genetic diagnosis of Gilbert's syndrome) or transaminases > 3.0x normal

4. Prior treatment with thalidomide or other imid drugs within previous 6 months

5. Prior treatment with bevacizumab (systemic or nasal) within previous 6 weeks

6. Prior treatment with pazopanib within previous 6 weeks

7. The use of octreotide or estrogens within the previous month

8. History of prior unprovoked thromboembolism confirmed by venous ultrasound or other imaging modalities

9. Peripheral neuropathy, confirmed by neurologic consultation

10. Known underlying hypoproliferative anemia (i.e. myelodysplasia, aplastic anemia)

11. Currently enrolled in other interventional trials

12. Known hypersensitivity to thalidomide or lenalidomide.

13. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

14. Known SMAD-4 mutation

15. Anything that in the investigator's opinion is likely to interfere with completion of the study