- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02287558
Pomalidomide in Hereditary Hemorrhagic Telangiectasia and Transfusion-Dependent Vascular Ectasia: a Phase I Study
July 13, 2020 updated by: Keith McCrae, The Cleveland Clinic
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
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.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
This is a single-arm, open-label study that will investigate the efficacy and safety profile of pomalidomide in patients with genetically-documented Hereditary Hemorrhagic Telangiectasia (defined by characteristic mutations in Eng, Alk-1 or Smad-4) or idiopathic vascular ectasia with no documented mutations, leading to refractory bleeding of the small bowel.
This study will be limited to patients with documented bleeding from the small bowel, including the duodenum, jejunum or ileum.
Eligible patients will be dependent on transfusion or intravenous iron therapy (requiring at least 4 units of blood transfusion or 4 iron infusions over the preceding 4 months) and will have endoscopically-confirmed areas of vascular ecstasia.
Therapy for all eligible patients will be initiated with a 1 mg daily dose of pomalidomide.
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 at the investigator's discretion to a maximal dose of 5 mg/day.
Cessation of GI bleeding will be defined as maintenance of stable hemoglobin without blood transfusion or intravenous iron therapy over a 4 week period.
Once GI bleeding has ceased, patients will be maintained at a stable pomalidomide dose for an additional 4 months, and the dose then tapered by 1 mg per month, or until bleeding recurs.
Patients will be followed for a total of six months post-therapy to determine whether the response is maintained.
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pomalidomide
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.
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Transfusion requirement measure
Time Frame: 8 months
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 27, 2015
Primary Completion (Actual)
June 1, 2019
Study Completion (Actual)
June 1, 2019
Study Registration Dates
First Submitted
November 6, 2014
First Submitted That Met QC Criteria
November 6, 2014
First Posted (Estimate)
November 10, 2014
Study Record Updates
Last Update Posted (Actual)
July 15, 2020
Last Update Submitted That Met QC Criteria
July 13, 2020
Last Verified
July 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Congenital Abnormalities
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Pathological Conditions, Anatomical
- Cardiovascular Abnormalities
- Vascular Malformations
- Telangiectasis
- Dilatation, Pathologic
- Telangiectasia, Hereditary Hemorrhagic
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Pomalidomide
Other Study ID Numbers
- CASE4Z14
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hereditary Hemorrhagic Telangiectasia
-
Vaderis Therapeutics AGRecruitingHereditary Hemorrhagic Telangiectasia (HHT)United States, Spain, France, Belgium, Netherlands, Italy
-
Unity Health TorontoSunnybrook Health Sciences Centre; University of Pittsburgh; Duke University; Barrow... and other collaboratorsActive, not recruitingHereditary Hemorrhagic Telangiectasia (HHT)Canada
-
Imperial College LondonCompletedHereditary Hemorrhagic Telangiectasia (HHT)United Kingdom
-
University Hospital, EssenCompletedHereditary Haemorrhagic Telangiectasia (HHT)Germany
-
University of PennsylvaniaCompletedHereditary Hemorrhagic Telangiectasia (HHT)United States
-
University Hospital, EssenCompleted
-
Centre Hospitalier Universitaire DijonCompletedHereditary Hemorrhagic TelangiectasiaFrance
-
Hospices Civils de LyonCompletedHHT | Hemorrhagic Hereditary TelangiectasiaFrance
-
Hospices Civils de LyonCompletedLiver Transplant | Hereditary Haemorrhagic Telangiectasia
-
Unity Health TorontoThe Hospital for Sick Children; Sunnybrook Health Sciences Centre; National Institute... and other collaboratorsCompletedHereditary Hemorrhagic TelangiectasiaCanada
Clinical Trials on Pomalidomide
-
Kirby InstituteActive, not recruitingHigh Grade Squamous Intra-epithelial Lesion (HSIL)Australia
-
Amsterdam UMC, location VUmcNot yet recruitingMultiple Myeloma | Multiple Myeloma in Relapse | Multiple Myeloma, Refractory
-
Multiple Myeloma Research ConsortiumEli Lilly and Company; GlaxoSmithKline; AbbVie; Takeda; Genentech, Inc.; Celgene Corporation and other collaboratorsRecruitingRelapsed Refractory Multiple MyelomaUnited States
-
CelgeneTerminatedSystemic Sclerosis | Scleroderma, Systemic | Systemic Scleroderma | Interstitial Lung Disease | Sclerosis, SystemicUnited States, Spain, France, Australia, Italy, Switzerland, Germany, Poland, United Kingdom, Russian Federation
-
Stanford UniversityCelgene CorporationWithdrawnPulmonary FibrosisUnited States
-
CelgeneCompletedMultiple MyelomaCanada, Denmark, Australia, Belgium, France, Germany, Italy, Netherlands, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, Czechia, Greece
-
CelgeneCompletedMultiple MyelomaBelgium, United Kingdom, Italy, Germany, Sweden, Denmark, Norway, Spain
-
Jiangsu Simcere Pharmaceutical Co., Ltd.Second Hospital of Shanxi Medical UniversityCompleted