Low-Dose Sirolimus for the Treatment of RUNX1 Familial Platelet Disorder

NCT07844694 | Recruiting Early Phase 1 FDA Drug

• 3 other identifiers: STUDY00028610NCI-2026-03902P30CA069533
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the safety and side effects of low-dose sirolimus in treating patients with RUNX1 familial platelet disorder (FPD). RUNX1-FPD is a rare inherited disorder with symptoms such as mild to moderately low platelet count, abnormal platelet function, and an increased risk of developing cancers like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is caused by changes (variants) in the RUNX1 gene that is passed down (inherited) from an affected parent. Sirolimus is typically given to help prevent organ rejection in patients receiving kidney transplants. However, sirolimus may also be able to prevent RUNX1-FPD from progressing to cancers like MDS and AML by targeting another protein called mTORC1. Sirolimus may be a safe treatment for patients with RUNX1-FPD.

Conditions

Familial Platelet Disorder With Associated Myeloid Malignancy

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3+ treatment-related adverse events (TRAEs)

  The incidence of grade 3+ TRAEs and the total proportion of participants who experienced grade 3+ TRAEs will be estimated and presented with the corresponding 95% exact Clopper Pearson confidence intervals.

  From study day 1 (week 1) to 30 days after the last dose of sirolimus

Secondary Outcomes (7)

• Change in platelet count

  From screening, pre dose on study day 1 (week 1) to end of treatment (EOT) (week 24, day 168)

• Change in variant allele frequency for existing clones

  From screening to end of study (EOS) (week 52, day 365)

• Change in number of clonal hematopoiesis of indeterminate potential mutations

  From screening to EOS (week 52, day 365)

• Change in percent positivity based on activated GPIIb IIIa and surface P selectin and CD42b

  From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)

• Change in aggregation from baseline based on thromboelastography (TEG)

  From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)

Study Arms (1)

Treatment (sirolimus)

EXPERIMENTAL

Patients receive sirolimus PO QD on days 1-168 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone marrow biopsy and/or aspiration throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Other: Questionnaire Administration; Drug: Sirolimus

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (sirolimus)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy/aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (sirolimus)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy/aspiration

Treatment (sirolimus)

Questionnaire Administration OTHER

Ancillary studies

Treatment (sirolimus)

Sirolimus DRUG

Given PO

Also known as: AY 22989, AY-22989, AY22989, RAPA, Rapamune, Rapamycin, SILA 9268A, SILA-9268A, SILA9268A, WY 090217, WY-090217, WY090217

Treatment (sirolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided signed, informed consent before initiation of any study specific procedures
• Aged ≥ 18 years at the time of signing the informed consent
• Confirmed pathogenic/likely pathogenic (P/LP) germline RUNX1 variant per ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) RUNX1-specific variant curation rules
• Patient must be willing to provide a bone marrow sample at time of screening and at the end of treatment with sirolimus
• Platelet count of ≥ 50,000/µL
• Creatinine clearance (CrCl) of ≥ 60 mL/min; estimated using the Cockcroft Gault formula or measured by 24 hour urine collection. Exceptions will be allowed, at the discretion of the investigator, for cases of a concomitant medication that alters renal function
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 × upper limit of normal (ULN)
• Total bilirubin \< 1.5 × ULN
• Left ventricular ejection fraction (EF) \> 50% or at the discretion of the investigator

You may not qualify if:

• Known allergy to sirolimus
• History of major bleeding events that are clinically relevant in the judgement of the investigator or non-major bleeding events that cannot be controlled using SOC practices
• Any known history of lymphoma, myelodysplastic syndrome (MDS), or other hematologic malignancy using International Working Group criteria
• Prior treatment with sirolimus or a rapalog, mTOR inhibitor, or B-cell-depleting therapy within 28 days before study day 1
• Treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4; e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, and clarithromycin), strong inducers of CYP3A4 (e.g., rifampin and rifabutin), other drugs that could increase sirolimus blood concentrations (e.g., bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors \[e.g., ritonavir, indinavir, boceprevir, and telaprevir\], metoclopramide, nicardipine, troleandomycin, and verapamil), other drugs that could decrease sirolimus blood concentrations (e.g., carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort \[Hypericum perforatum\]), or drugs with blood concentrations that could increase (e.g., verapamil) within 7 days before study day 1, or at the discretion of the investigator
• Use of cannabidiols that increase blood levels of sirolimus, within 7 days before study day 1 or at the discretion of the investigator
• Myocardial infarction within 6 months before study day 1, congestive heart failure (New York Heart Association \> class II)
• Total cholesterol \> 300 mg/dL or triglyceride \> 400 mg/dL
• Arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months before study day 1
• Infection requiring intravenous anti-infective treatment within 1 week of study day 1
• Live vaccines (e.g., measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin \[BCG\], yellow fever, varicella, and TY21a typhoid) within 28 days before study day 1
• The enrollment of a patient with a history of infection with hepatitis B virus (HBV) but with undetectable HBV deoxyribonucleic acid (DNA) by standard institutional testing can be considered after consultation with the investigator
• Patients with history of chronic hepatitis C virus (HCV) must have documentation of completed curative standard of care (SOC) antiviral therapy
• Patients with history of HIV infection must be well-managed with SOC antiretroviral therapy (highly active antiretroviral therapy \[HAART\])
• Patients with history of Epstein-Barr may be considered after consultation with the treating physician

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: collaborator
• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Platelet Disorder, Familial, with Associated Myeloid Malignancy

Interventions

Specimen Handling; Biopsy; Sirolimus

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Macrolides; Lactones; Organic Chemicals

Study Officials

• Curtis A Lachowiez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Regina Samson

CONTACT

503-494-0793; samsonan@ohsu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 28, 2026
• Study Start: September 30, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 28, 2026

Record last verified: 2026-09

Locations

US (1)