A Study to Evaluate Pomalidomide to Treat Bleeding in Hereditary Hemorrhagic Telangiectasia (HHT)

Overview

About this study

The purpose of this study is to evaluate pomalidomide vs. placebo 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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, unless there has been a colonoscopy with normal (negative)
results, or in which the patient has had no more than 5 small (in the opinion of the
gastroenterologist) colonic polyps completely removed within the preceding 18 months

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

Eligibility last updated 6/1/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Vivek Iyer, M.D., M.P.H.

Open for enrollment

Contact information:

Sue Ann Donlinger

(507) 284-9259

Donlinger.SueAnn@mayo.edu

More information

Publications

  • Hereditary hemorrhagic telangiectasia (HHT) is characterized by frequent severe bleeding, particularly epistaxis, and life-threatening complications including stroke, brain abscess and heart failure. The psychological impact of HHT is not known. We conducted this cross sectional study to determine the prevalence of depression and post-traumatic stress disorder (PTSD) related to HHT. Read More on PubMed
  • Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs) in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β) signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curaçao) diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed. Read More on PubMed
  • Hereditary hemorrhagic telangiectasia (HHT)-related epistaxis leads to alterations in social functioning and quality of life. Although more than 95% experience epistaxis, there is considerable variability of severity. Because no standardized method exists to measure epistaxis severity, the purpose of this study was to determine factors associated with patient-reported severity to develop a severity score. Read More on PubMed