Actively Recruiting
Phase Ib Study of Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
Led by National Cancer Institute (NCI) · Updated on 2026-06-03
75
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying the effects of imatinib in adults with inherited RUNX1 gene mutations, which are linked to blood cell formation problems, bleeding tendencies, and a higher risk of blood cancers. This phase Ib study aims to find the best dose of imatinib to increase RUNX1 activity and assess changes in platelet function and inflammation. Participants include those with pathogenic RUNX1 mutations and healthy controls without these mutations. The study has two treatment groups receiving imatinib at different doses and one control group for blood and marrow sample collection without treatment. Imatinib is taken orally once daily for either 28 days (dose escalation phase) or up to 84 days (dose expansion phase). Participants undergo blood tests every two weeks, heart function tests, and may have bone marrow biopsies at the start and end of treatment. Questionnaires about symptoms and well-being are completed during the study. Participants will have follow-up visits at home or the study site 30 days after stopping imatinib. The study monitors drug safety, pharmacokinetics, platelet structure and function, and inflammatory markers throughout. Healthy volunteers and unaffected family members participate with one clinic visit for blood tests and questionnaires. The total study duration varies depending on treatment group and includes screening, treatment, and follow-up periods.
CONDITIONS
Brief Title
Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Confirmed pathogenic or likely pathogenic germline RUNX1 mutation for affected participants
- History of significant bleeding or abnormal platelet function tests for affected participants
- Bone marrow evaluation within 12 months before starting imatinib for affected participants
- Adequate organ and marrow function as defined by specific blood counts and lab values
- ECOG performance status of 2 or less (Karnofsky 60% or higher)
- Ability and willingness to use effective contraception if of child-bearing potential
- Willingness to sign informed consent
- Unaffected family members or healthy volunteers without RUNX1 mutation for control group
- No platelet-inhibiting medications taken within 2 weeks before enrollment for all participants
You will not qualify if you...
- Current use of other investigational agents
- Prior therapy directed at hematologic malignancies
- Medications affecting platelet number or function (e.g., aspirin)
- Lack of access to medical care at home
- Pregnancy confirmed by testing
- Presence of imatinib-resistant ABL mutations in affected participants
- Allergic reactions to imatinib or similar compounds
- Use of medications that interfere with imatinib metabolism (CYP3A4 inhibitors or inducers)
- Uncontrolled illnesses that increase risk or limit study compliance
- Cardiac conditions including symptomatic heart failure, unstable angina, or arrhythmias for affected participants
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 28 days for dose escalation; up to 12 weeks for dose expansion
Participants with pathogenic or likely pathogenic germline RUNX1 mutations receive daily oral imatinib at escalating doses for 28 days in the dose escalation phase or at the maximum tolerated dose for up to 12 weeks in the dose expansion phase.
Visits during dosing and pharmacokinetic/pharmacodynamic evaluations at baseline and Day 84 for expansion phase participants
Duration - Up to 28 days after treatment
Participants are monitored for safety and outcomes after completing imatinib treatment during the expansion phase.
Follow-up visits to assess safety and treatment effects
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
R
Rebecca B Alexander
L
Lea C Cunningham, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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