Pomalidomide in Hereditary Hemorrhagic Telangiectasia and Transfusion-Dependent Vascular Ectasia: a Phase I Study

NCT02287558 | Completed Phase 1 DMC

• 1 other identifier: CASE4Z14
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate patients \> 18 years of age with transfusion-dependent gastrointestinal bleeding due to documented gastrointestinal vascular ectasia with or without concurrent hereditary hemorrhagic telangiectasia (HHT). This study will focus on documented bleeding sites in the small bowel, including the duodenum, jejunum and ileum. Eligible patients will have endoscopically-documented sites of vascular ectasia and will have required at least 4 units of blood transfusion or episodes of intravenous iron administration over the preceding four months.

Conditions

Hereditary Hemorrhagic Telangiectasia; Idiopathic Vascular Ectasia

Keywords

HHT; CASE4Z14; Pomalidomide

Outcome Measures

Primary Outcomes (1)

• Transfusion requirement measure

  To compare the requirement for transfusion and intravenous iron administration in individual patients in the 4 month period before initiation of pomalidomide with that over a 4 month period following pomalidomide therapy.

  8 months

Study Arms (1)

Pomalidomide

EXPERIMENTAL

Pomalidomide will be supplied as 1.0 mg, 2.0 mg, 3.0 mg and 4.0 mg capsules for oral administration. The principal investigator will determine whether intrapatient dose escalation is indicated based on the response of the patient's bleeding during the first 30 days of therapy. If dose escalation is indicated, pomalidomide will be increased by 1 mg/month at the investigator's discretion to a maximal dose of 5 mg/day.

Drug: Pomalidomide

Interventions

Pomalidomide DRUG

Also known as: Pomalyst, CC-4047, Imnovid

Pomalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Transfusion of at least 4 units of blood and/or four doses of intravenous iron over the preceding four months.
• Recurrent bleeding after at least one previous interventional endoscopic procedure
• Platelet count ≥ 125,000/µl
• WBC ≥ 4,000/µl
• Normal prothrombin (PT) and activated partial thromboplastin time (aPTT)
• Endoscopically-documented angiodysplasia and/or arteriovenous malformations involving the small bowel
• 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.
• Ability to understand and sign informed consent
• 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

You may not qualify if:

• 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.
• Breast feeding
• Renal insufficiency, serum creatinine \> 2.0 mg/dl
• Hepatic insufficiency, bilirubin \> 2.0 or transaminases \> 3.0 x normal
• Previous treatment with Thalidomide or other imid drugs within previous 12 months
• History of prior thromboembolism with known thrombophilia
• Peripheral neuropathy, as determined from neurologic consultation
• Underlying hypoproliferative anemia (i.e. myelodysplasia)
• Inherited or significant acquired coagulopathy (i.e. hemophilia, advanced liver disease)
• Chronic aspirin, NSAID therapy, anticoagulation therapy or antiplatelet agents
• Currently enrolled in other interventional trials
• Known hypersensitivity to thalidomide or lenalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, or similar drugs.
• Anything that in the investigator's opinion is likely to interfere with completion of the study † A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Keith McCrae, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Benign Hematology

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 10, 2014
• Study Start: January 27, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 15, 2020

Record last verified: 2020-07

Locations

US (1)