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

Primary Purpose

Hereditary Hemorrhagic Telangiectasia, Idiopathic Vascular Ectasia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pomalidomide
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Hemorrhagic Telangiectasia focused on measuring HHT, CASE4Z14, Pomalidomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age > 18 years
  2. Transfusion of at least 4 units of blood and/or four doses of intravenous iron over the preceding four months.
  3. Recurrent bleeding after at least one previous interventional endoscopic procedure
  4. Platelet count ≥ 125,000/µl
  5. WBC ≥ 4,000/µl
  6. Normal prothrombin (PT) and activated partial thromboplastin time (aPTT)
  7. Endoscopically-documented angiodysplasia and/or arteriovenous malformations involving the small bowel
  8. 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.
  9. Ability to understand and sign informed consent
  10. 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:

  1. 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.

  2. Breast feeding
  3. Renal insufficiency, serum creatinine > 2.0 mg/dl
  4. Hepatic insufficiency, bilirubin > 2.0 or transaminases > 3.0 x normal
  5. Previous treatment with Thalidomide or other imid drugs within previous 12 months
  6. History of prior thromboembolism with known thrombophilia
  7. Peripheral neuropathy, as determined from neurologic consultation
  8. Underlying hypoproliferative anemia (i.e. myelodysplasia)
  9. Inherited or significant acquired coagulopathy (i.e. hemophilia, advanced liver disease)
  10. Chronic aspirin, NSAID therapy, anticoagulation therapy or antiplatelet agents
  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. 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).

Sites / Locations

  • Cleveland Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pomalidomide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
November 6, 2014
Last Updated
July 13, 2020
Sponsor
The Cleveland Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT02287558
Brief Title
Pomalidomide in Hereditary Hemorrhagic Telangiectasia and Transfusion-Dependent Vascular Ectasia: a Phase I Study
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
January 27, 2015 (Actual)
Primary Completion Date
June 1, 2019 (Actual)
Study Completion Date
June 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Hemorrhagic Telangiectasia, Idiopathic Vascular Ectasia
Keywords
HHT, CASE4Z14, Pomalidomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pomalidomide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
Pomalyst, CC-4047, Imnovid
Primary Outcome Measure Information:
Title
Transfusion requirement measure
Description
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.
Time Frame
8 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith McCrae, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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