Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02287558
Recruitment Status : Recruiting
First Posted : November 10, 2014
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Keith McCrae, The Cleveland Clinic

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.

Condition or disease Intervention/treatment Phase
Hereditary Hemorrhagic Telangiectasia Idiopathic Vascular Ectasia Drug: Pomalidomide Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 27, 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019


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.
Drug: Pomalidomide
Other Names:
  • Pomalyst
  • CC-4047
  • Imnovid




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02287558


Contacts
Layout table for location contacts
Contact: Lindsey Clark 216-445-9048 clarkl@ccf.org
Contact: Linda McCowen, RN 216-444-7698 mccowel@ccf.org

Locations
Layout table for location information
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Kill Ashley, RN    216-444-2774    resha@ccf.org   
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Layout table for investigator information
Principal Investigator: Keith McCrae, MD The Cleveland Clinic

Layout table for additonal information
Responsible Party: Keith McCrae, Director of Benign Hematology, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02287558     History of Changes
Other Study ID Numbers: CASE4Z14
First Posted: November 10, 2014    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018

Keywords provided by Keith McCrae, The Cleveland Clinic:
HHT
CASE4Z14
Pomalidomide

Additional relevant MeSH terms:
Layout table for MeSH terms
Telangiectasis
Dilatation, Pathologic
Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Pomalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents