Inherited Bone Marrow Failure SyndromePhase 1NCT06090669
Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
A Phase 1 study testing TruSight Oncology and imatinib in people with Inherited Bone Marrow Failure Syndrome and Familial Platelet Disorder With Predisposition to Myeloid Malignancies, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes. Read more about this study
- Who is it for?
- Ages 18 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Inherited Bone Marrow Failure Syndrome, Familial Platelet Disorder With Predisposition to Myeloid Malignancies
- What is being tested?
- TruSight Oncology and imatinib
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2023to 30 Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 to 120 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- --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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: Phase Ib Study of Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
Background:
Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes.
Read more
Objective:
The purpose of the study includes determining which dose of imatinib is best for people with pathogenic or likely pathogenic RUNX1 mutations without blood cancers, and to determine whether there are any changes in platelet function and inflammatory markers.
Eligibility:
Adults aged 18 and older with RUNX1 mutations. Healthy people without this mutation, including family members of affected participants, are also needed.
Design:
Participants with the RUNX1 mutation will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They may need a new bone marrow biopsy if they haven't had one in the past year.
Imatinib is a tablet taken by mouth once a day, every day, at home. Affected participants in different parts of the study will take imatinib for either 42 days or up to 98 days. They will fill out questionnaires about how they are feeling.
For the first part of the study, participants will have blood tests every 2 weeks, either at home or at the NIH, while they are taking the imatinib. They will have a follow up visit, at home or at the NIH, when they are done taking imatinib on Day 42.
Participants on the second part of the study will come to NIH on days 1 and days 98. They will have blood tests every 2 weeks (at home or the NIH) while they are taking imatinib. They may opt to have a bone marrow biopsy repeated after they finish their course of imatinib.
Participants will have a follow-up visit (at home or the NIH) 30 days after they stop taking imatinib.
Participants who do not have the RUNX1 mutation will have 1 clinic visit. They will have blood tests. They will fill out questionnaires. They may opt to have a bone marrow biopsy.
Read the detailed description
Background:
- Runt-related transcription factor 1 (RUNX1) gene is located on chromosome 21 and encodes an important regulator of hematopoiesis. People normally inherit one functional copy from each parent.
- RUNX1 function is highly dose dependent as both too little as well as too much RUNX1 activity is associated with development of hematologic malignancy. The focus of this protocol is participants with germline RUNX1 mutations resulting in too little RUNX1 activity.
- Germline heterozygous RUNX1 mutations are inherited in an autosomal dominant manner and cause a disorder called Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM). Patients with one deleterious germline RUNX1 mutation often have haploinsufficiency although some mutations are associated with a dominant negative effect.
- Clinically, patients with germline RUNX1 mutations have aberrant megakaryocytic development, which often results in quantitative and/or qualitative platelet defects. Patients often have easy bleeding or bruising, although some cases are subclinical, and they may present to clinicians with hematologic malignancy.
- Patients with germline RUNX1 mutations have 35-45% lifetime risk of developing myeloid hematologic malignancies including MDS and AML. Increased risk of B-ALL, T-ALL and other hematologic malignancies is also associated with deleterious germline RUNX1 mutations.
- Deleterious RUNX1 mutations are known to be associated with high-risk malignancy with poor response to upfront chemotherapy and require hematopoietic stem cell transplantation (HSCT).
- Imatinib is an ABL inhibitor (with some SFK inhibition) that is FDA approved and indicated for treatment of CML, ALL, MDS/MPD, aggressive systemic mastocytosis (ASM) as well as hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL).
- ABL physically associates with RUNX1, phosphorylates key tyrosines within the RUNX1 inhibitory domain and negatively regulates RUNX1 transcriptional activity.
- We hypothesize that imatinib will decrease RUNX1 tyrosine phosphorylation thereby increasing RUNX1 protein activity to a level closer to that expected for 2 normal copies of RUNX1. We also hypothesize that normal levels of RUNX1 protein activity will ameliorate platelet dysfunction and bleeding symptoms via objective measures.
- We expect this study to inform the biologically relevant endpoints for a subsequent phase II efficacy study, which would also seek to determine if longer term imatinib administration could prevent malignant transformation.
Objectives:
- To determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose ramp-up phase
- To determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phase
Eligibility:
- Age >=18 years
- Participants with deleterious germline RUNX1 mutations as defined by ClinGen with adequate organ function and no history of hematologic malignancy.
Design:
- This is a phase Ib study with 2 cohorts (participants with and without pathogenic or likely pathogenic RUNX1 mutations) and 3 arms (2 for imatinib administration and 1 for biobanking control).
- A non-randomized dose-ramp-up design will be used in the first arm for participants with pathogenic or likely pathogenic germline RUNX1 mutations. Participants will begin imatinib at 100 mg orally daily (ramp up dose for 14 days) and then the dose will increase to 200 mg daily for 4 weeks. Participants unable to tolerate imatinib 200 mg daily will have their dose reduced to 100 mg daily.
- Participants will have PK/PD evaluations during Arm 2 (expansion phase).
- An expansion cohort will be treated at the maximum tolerated dose (MTD) in Arm 2 (100 mg or 200 mg), daily for 12 weeks after receiving a ramp-up dose (100mg) for 14 days. Participants who are treated on the dose ramp up phase may also be treated in the expansion phase after an appropriate wash out period of 28 days.
- The third arm is for unaffected family control participants with wildtype RUNX1 or healthy volunteers who may choose to enroll to donate blood or marrow but will not be treated.
- Up to 6 evaluable participants will be enrolled for dose ramp up, 12 participants in the expansion cohort, and up to 25 unaffected controls contemporaneously whenever feasible.
- Conditions
- Inherited Bone Marrow Failure Syndrome, Familial Platelet Disorder With Predisposition to Myeloid Malignancies
- Being tested
- TruSight Oncology, imatinib
- Keywords
- predisposition to hematologic malignancies, germline mutations, IBMFS
- Medical subject headings
- Congenital Bone Marrow Failure Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TruSight OncologyDevice
Assay sequencing platform to identify pathogenic genetic mutations in DNA and RNA
imatinibDrug
Imatinib at 100-200 mg PO QD based on arm assignment/dose level
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and ramp-up | Experimental | Escalating and ramping up doses of imatinib to determine the MTD Receives: Device: TruSight Oncology; Drug: imatinib |
| Dose Expansion | Experimental | Imatinib at the MTD Receives: Device: TruSight Oncology; Drug: imatinib |
| No Treatment | No intervention | Collection of blood or marrow only. No treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phase
Safety will be evaluated by the number of DLTs identified at each dose level.
Measured: Arm 1 for 1 month and Arm 2 for 3 months
Determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose ramp up phase
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.
Measured: Arm 1 for 1 month and Arm 2 for 3 months
Secondary outcomes (4)
Safety of imatinib in the dose escalation and ramp-up phase
AEs are reported by type and grade, and frequency.
Measured: Assessed from Day 1 of study drug through 28 days (escalation) and 42 days (ramp-up) after the first dose.
Change in platelet qualitative defects
Change in measurement; assessed for potential differences in their study results before and after imatinib administration by an appropriate paired test.
Measured: Measured at baseline (Day 1- both arms) and Day 42 for Arm 1 and Day 98 for Arm 2
Improvement in platelet dense granule structure by electron microscopy as compared to baseline in the dose expansion phase
Change in measurement; assessed for potential differences in their study results before and after imatinib administration by an appropriate paired test.
Measured: Measured at baseline (Day 1- both arms) and Day 98 for Arm 2
Pharmacokinetics of imatinib in the RUNX1 population in the dose expansion phase
Change in measurement of drug levels in blood; assessed for potential differences in their study results before and after imatinib administration by an appropriate paired test.
Measured: Measured at baseline (Day 1) and Day 98 for Arm 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2023
- Study start19 Dec 2023
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inherited Bone Marrow Failure SyndromeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lea C Cunningham, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06090669
- Sponsor's protocol ID
- 10001542
- Other IDs
- 001542-C
- Status last verified
- 28 Oct 2026
- First submitted
- 17 Oct 2023
- Last updated
- 30 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.@@@@@@
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency
- ClinicalTrials.gov ID
- NCT06090669
- Acronym / sponsor ID
- 10001542
- Conditions
- Inherited Bone Marrow Failure Syndrome, Familial Platelet Disorder With Predisposition to Myeloid Malignancies
- Keywords
- predisposition to hematologic malignancies, germline mutations, IBMFS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Dec 2023 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Oct 2027 (estimated)
- First posted
- 19 Oct 2023 (actual)
- 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.
Background:
Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes.
Objective:
The purpose of the study includes determining which dose of imatinib is best for people with pathogenic or likely pathogenic RUNX1 mutations without blood cancers, and to determine whether there are any changes in platelet function and inflammatory markers.
Eligibility:
Adults aged 18 and older with RUNX1 mutations. Healthy people without this mutation, including family members of affected participants, are also needed.
Design:
Participants with the RUNX1 mutation will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They may need a new bone marrow biopsy if they haven't had one in the past year.
Imatinib is a tablet taken by mouth once a day, every day, at home. Affected participants in different parts of the study will take imatinib for either 42 days or up to 98 days. They will fill out questionnaires about how they are feeling.
For the first part of the study, participants will have blood tests every 2 weeks, either at home or at the NIH, while they are taking the imatinib. They will have a follow up visit, at home or at the NIH, when they are done taking imatinib on Day 42.
Participants on the second part of the study will come to NIH on days 1 and days 98. They will have blood tests every 2 weeks (at home or the NIH) while they are taking imatinib. They may opt to have a bone marrow biopsy repeated after they finish their course of imatinib.
Participants will have a follow-up visit (at home or the NIH) 30 days after they stop taking imatinib.
Participants who do not have the RUNX1 mutation will have 1 clinic visit. They will have blood tests. They will fill out questionnaires. They may opt to have a bone marrow biopsy.
Detailed description
Background:
- Runt-related transcription factor 1 (RUNX1) gene is located on chromosome 21 and encodes an important regulator of hematopoiesis. People normally inherit one functional copy from each parent.
- RUNX1 function is highly dose dependent as both too little as well as too much RUNX1 activity is associated with development of hematologic malignancy. The focus of this protocol is participants with germline RUNX1 mutations resulting in too little RUNX1 activity.
- Germline heterozygous RUNX1 mutations are inherited in an autosomal dominant manner and cause a disorder called Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM). Patients with one deleterious germline RUNX1 mutation often have haploinsufficiency although some mutations are associated with a dominant negative effect.
- Clinically, patients with germline RUNX1 mutations have aberrant megakaryocytic development, which often results in quantitative and/or qualitative platelet defects. Patients often have easy bleeding or bruising, although some cases are subclinical, and they may present to clinicians with hematologic malignancy.
- Patients with germline RUNX1 mutations have 35-45% lifetime risk of developing myeloid hematologic malignancies including MDS and AML. Increased risk of B-ALL, T-ALL and other hematologic malignancies is also associated with deleterious germline RUNX1 mutations.
- Deleterious RUNX1 mutations are known to be associated with high-risk malignancy with poor response to upfront chemotherapy and require hematopoietic stem cell transplantation (HSCT).
- Imatinib is an ABL inhibitor (with some SFK inhibition) that is FDA approved and indicated for treatment of CML, ALL, MDS/MPD, aggressive systemic mastocytosis (ASM) as well as hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL).
- ABL physically associates with RUNX1, phosphorylates key tyrosines within the RUNX1 inhibitory domain and negatively regulates RUNX1 transcriptional activity.
- We hypothesize that imatinib will decrease RUNX1 tyrosine phosphorylation thereby increasing RUNX1 protein activity to a level closer to that expected for 2 normal copies of RUNX1. We also hypothesize that normal levels of RUNX1 protein activity will ameliorate platelet dysfunction and bleeding symptoms via objective measures.
- We expect this study to inform the biologically relevant endpoints for a subsequent phase II efficacy study, which would also seek to determine if longer term imatinib administration could prevent malignant transformation.
Objectives:
- To determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose ramp-up phase
- To determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phase
Eligibility:
- Age >=18 years
- Participants with deleterious germline RUNX1 mutations as defined by ClinGen with adequate organ function and no history of hematologic malignancy.
Design:
- This is a phase Ib study with 2 cohorts (participants with and without pathogenic or likely pathogenic RUNX1 mutations) and 3 arms (2 for imatinib administration and 1 for biobanking control).
- A non-randomized dose-ramp-up design will be used in the first arm for participants with pathogenic or likely pathogenic germline RUNX1 mutations. Participants will begin imatinib at 100 mg orally daily (ramp up dose for 14 days) and then the dose will increase to 200 mg daily for 4 weeks. Participants unable to tolerate imatinib 200 mg daily will have their dose reduced to 100 mg daily.
- Participants will have PK/PD evaluations during Arm 2 (expansion phase).
- An expansion cohort will be treated at the maximum tolerated dose (MTD) in Arm 2 (100 mg or 200 mg), daily for 12 weeks after receiving a ramp-up dose (100mg) for 14 days. Participants who are treated on the dose ramp up phase may also be treated in the expansion phase after an appropriate wash out period of 28 days.
- The third arm is for unaffected family control participants with wildtype RUNX1 or healthy volunteers who may choose to enroll to donate blood or marrow but will not be treated.
- Up to 6 evaluable participants will be enrolled for dose ramp up, 12 participants in the expansion cohort, and up to 25 unaffected controls contemporaneously whenever feasible.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and ramp-up | Experimental | Device: TruSight Oncology, Drug: imatinibEscalating and ramping up doses of imatinib to determine the MTD |
| Dose Expansion | Experimental | Device: TruSight Oncology, Drug: imatinibImatinib at the MTD |
| No Treatment | No intervention | –Collection of blood or marrow only. No treatment. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (12 listed)
- 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).
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 |
|---|---|---|
| TruSight OncologyAssay sequencing platform to identify pathogenic genetic mutations in DNA and RNA | Device | Dose Escalation and ramp-up, Dose Expansion |
| imatinibImatinib at 100-200 mg PO QD based on arm assignment/dose level | Drug | Dose Escalation and ramp-up, Dose Expansion |
Primary outcome
Determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phase
Time frame: Arm 1 for 1 month and Arm 2 for 3 months
Safety will be evaluated by the number of DLTs identified at each dose level.
Determine the dose of imatinib for dose expansion in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose ramp up phase
Time frame: Arm 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.
4 secondary outcomes
Safety of imatinib in the dose escalation and ramp-up phase
Time frame: Assessed from Day 1 of study drug through 28 days (escalation) and 42 days (ramp-up) after the first dose.
Change in platelet qualitative defects
Time frame: Measured at baseline (Day 1- both arms) and Day 42 for Arm 1 and Day 98 for Arm 2
Improvement in platelet dense granule structure by electron microscopy as compared to baseline in the dose expansion phase
Time frame: Measured at baseline (Day 1- both arms) and Day 98 for Arm 2
Pharmacokinetics of imatinib in the RUNX1 population in the dose expansion phase
Time frame: Measured at baseline (Day 1) and Day 98 for Arm 2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.@@@@@@
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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.
Lea C Cunningham, M.D. principal investigator
National Cancer Institute (NCI)
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 TruSight Oncology and imatinib in people with Inherited Bone Marrow Failure Syndrome and Familial Platelet Disorder With Predisposition to Myeloid Malignancies, run by National Cancer Institute (NCI) 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 24 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 30 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Danielle F Pinkiert, R.N. ((240) 858-7566, danielle.pinkiert@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the safety of imatinib in participants with pathogenic or likely pathogenic germline RUNX1 mutations during the dose expansion phase (time frame: Arm 1 for 1 month and Arm 2 for 3 months). The study lists 2 primary outcomes in all. 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 30 Oct 2026.