Hereditary Hemorrhagic TelangiectasiaPhase 1NCT02287558
Pomalidomide in Hereditary Hemorrhagic Telangiectasia and Transfusion-Dependent Vascular Ectasia: a Phase I Study
A Phase 1 study testing Pomalidomide in people with Hereditary Hemorrhagic Telangiectasia and Idiopathic Vascular Ectasia, run by The Cleveland Clinic at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia, Idiopathic Vascular Ectasia
- What is being tested?
- Pomalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2015to 1 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read the 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.
- Being tested
- Pomalidomide
- Keywords
- HHT, CASE4Z14, Pomalidomide
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PomalidomideDrug
Also called Pomalyst, CC-4047, Imnovid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2014 (estimated)
- Study start27 Jan 2015
- Primary completion1 Jun 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keith McCrae, The Cleveland Clinic
- Investigators
- Keith McCrae, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02287558
- Sponsor's protocol ID
- CASE4Z14
- Status last verified
- Jul 2020
- First submitted
- 6 Nov 2014
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02287558
- Acronym / sponsor ID
- CASE4Z14
- Keywords
- HHT, CASE4Z14, Pomalidomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 27 Jan 2015 (actual)
- Primary completion
- 1 Jun 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 10 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide | Experimental | Drug: PomalidomidePomalidomide 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PomalidomideAlso: Pomalyst, CC-4047, Imnovid | Drug | Pomalidomide |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith McCrae, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pomalidomide in people with Hereditary Hemorrhagic Telangiectasia and Idiopathic Vascular Ectasia, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transfusion requirement measure (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.