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:

A clinical diagnosis of HHT as defined by the Curacao criteria.
Age > 18 years old.
Platelet count ≥ 100 x 10^9 /L.
WBC ≥ 2.5 x 10^9 /L.
INR ≤ 1.4 and normal ± 2 sec activated partial thromboplastin time by local laboratory criteria (aPTT).
Epistaxis severity score ≥ 3 measured over the preceding three months, measured at the screening visit.
A requirement for parenteral infusion of at least 250 mg of iron or transfusion of 1 unit of blood over the 24 weeks preceding the screening visit.
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.
Females of childbearing potential (FCBP)† must adhere to the pregnancy testing schedule mandated by the POMALYST REMS® program.
Ability to understand and sign informed consent.

†A female of childbearing poteintial is a sexually mature woman who:

has not undergone a hysterectomy or bilateral oophorectomy; or
has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Exclusion Criteria:

Women currently breastfeeding or pregnant.
Renal insufficiency, serum creatinine > 2.0 mg/dl.
Hepatic insufficiency, bilirubin > 2.0 (or > 4.0 in the setting of a prior clinical or genetic diagnosis of Gilbert's syndrome) or transaminases > 3.0 x normal.
Prior treatment with thalidomide or other Immunomodulatory imide drugs (IMiDs) within previous 6 months.
Prior treatment with bevacizumab (systemic or nasal) within previous 6 weeks.
The use of octreotide or estrogens within the previous month.
History of prior unprovoked thromboembolism confirmed by venous ultrasound or other imaging modalities.
Known peripheral neuropathy, confirmed by neurologic consultation.
Known underlying hypoproliferative anemia (i.e., myelodysplasia, aplastic anemia).
Currently enrolled in other interventional trials.
Known hypersensitivity to thalidomide or lenalidomid.

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
Rochester, Minn. Mayo Clinic principal investigator Vivek Iyer, M.D., M.P.H.	Closed for enrollment

Mayo Clinic Location

Status

Rochester, Minn.

Mayo Clinic principal investigator

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

Closed for enrollment

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

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