Imatinib for Inherited Bone Marrow Failure Syndrome with RUNX1 Deficiency
This study is testing a medication called imatinib to see if it can help people with a genetic condition called germline RUNX1 deficiency. This condition can cause easy bleeding or bruising and increases the risk of blood cancers. Researchers want to find the best dose of imatinib (300-400 mg daily) and check its safety. To join, you must be an adult (18-120 years old) with a confirmed RUNX1 gene mutation and a history of significant bleeding. The study aims to understand how imatinib affects platelet function and inflammation in people with this condition. The current status of this study is unclear, and it plans to enroll 75 participants.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 75 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoints for dose determination and safety are measured at 1 month for Arm 1 and 3 months for Arm 2.
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NCT06090669
Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~75 participants
Updated 2026-08-07 on ClinicalTrials.gov
What's tested:imatinibTruSight Oncology
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose escalation phase
Measured over Arm 1 for 1 month and Arm 2 for 3 months
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Lea C Cunningham, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Affected participants must have a confirmed pathogenic or likely pathogenic germline RUNX1 variant by history. ClinGen expert variant curation panel criteria for pathogenicity will be utilized.
Affected participants must have a history of clinically significant bleeding as defined by history of abnormal ISTH-BAT score, use of anti-bleeding medications (e.g., amicar), history of platelet transfusion, abnormal PFA screen, abnormal TEG, abnormal platelet aggregation or abnormal platelet electron microscopy.
Bone marrow morphology, flow cytometry and cytogenetics confirmed by the NIH Department of Laboratory Medicine (DLM) at least within 12 months of initiating imatinib.
TSO500 performed by NCI Lab of Pathology within 12 months of initiating imatinib.
Substantial GI malabsorption is not suspected.
Participants with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial if their HAART medications do not interact with imatinib.
Participants with evidence of chronic hepatitis B virus (HBV) infection, on suppressive therapy with undetectable HBV viral load are eligible for this trial. Suppressive therapy medication may not interact with imatinib.
Participants with a distant history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment, with undetectable HCV viral load are eligible. If unknown HCV is detected upon screening- these participants will not be eligible for the study.
Unaffected family members or healthy volunteers without RUNX1 mutation by pedigree or molecular testing Only participants who are related to the proband need to provide a molecular test.
The last dosage of any platelet inhibiting medications was at least 2 weeks prior to enrollment and research sample acquisition.
Age \>=18 years.
ECOG performance status \<=2 (Karnofsky \>=60%).
Participants must have adequate organ and marrow function as defined below:
leukocytes \>= 3,000/mcL
absolute neutrophil count \>= 1,500/mcL
platelets \>= 50,000/mcL (without transfusion support)
total bilirubin within normal institutional limits or \<= 3 X the institutional upper limit of normal for participants with Gilbert s syndrome
AST(SGOT)/ALT(SGPT) \<= 2.5 X institutional upper limit of normal
creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal.
NIDDK CKD-EPI equation GFR = 141 x min (Scr /kappa, 1)\^alpha x max(Scr /kappa, 1)\^-1.209 x 0.993\^Age x 1.018 \[if female\] x 1.159 \[if black\] where: Scr is serum creatinine in mg/dL, kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /kappa or 1, and max indicates the maximum of Scr /kappa or 1.
Note: GFR is expressed in mL/min per 1.73 m\^2, Scr is serum creatinine expressed in mg/dL, age is expressed in years, kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /kappa or 1, and max indicates the maximum of Scr /kappa or 1. Race is self-identified.
Women of child-bearing potential and men must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after the last administration of study drug.
Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 30 days after the last administration of study drug
Ability of participant to understand and the willingness to sign a written informed consent document.
Exclusion
Participants who are receiving any other investigational agents.
Participants who received prior hematologic malignancy directed therapy
Participants receiving medication that would affect platelet number or function (e.g., aspirin and anti-platelet medications
Participants without access to medical care at home.
Pregnancy (confirmed with beta-HCG serum or urine pregnancy test performed in females of childbearing potential at screening).
Participants with the following pathogenic/likely pathogenic abl mutations on baseline Illumina TSO500 testing of any detectable VAF within 12 months of receiving the first dose of imatinib
Abl mutations resistant to imatinib (T315I, F317L/V/C, T315A, V299L, Y253H, E255V/K, F359V/I/C)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or other agents used in study.
Concomitant medications that include the following:
Participants requiring medications which are inhibitors or inducers of CYP3A4 metabolism, as these may change imatinib plasma levels.
Uncontrolled intercurrent illness evaluated by history, physical exam, and chemistries or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant
Participants with the following cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
What this trial measures
- Determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose escalation phaseArm 1 for 1 month and Arm 2 for 3 months
Safety will be evaluated by the number of DLTs identified at each dose level. The number of DLTs at each dose level will be reported and used to determine the RP2D.
- Determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phaseArm 1 for 1 month and Arm 2 for 3 months
Safety will be evaluated by the number of DLTs identified at each dose level.