Recruiting

Early Phase 1

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

Sponsor:

OHSU Knight Cancer Institute

Code:

NCT07844694

Conditions

Familial Platelet Disorder With Associated Myeloid Malignancy

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Questionnaire Administration

Sirolimus

Study Details

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

Study ID

NCT07844694

Start date

Sep 30, 2026

Status verified date

Sep, 2026

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Jun 30, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

Exclusion Criteria:

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
Known diagnosis of tuberculosis is exclusionary to provide protection against reactivation of infections by the immunosuppressive activity of the study drug sirolimus

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
Participants who are pregnant may become pregnant, or who are breastfeeding

Because adequate and well-controlled studies of the impact of sirolimus on fetuses currently do not exist, study approved contraception must be used from start of study therapy to 12 weeks after the last dose of sirolimus
Adequate and well-controlled studies of infants fed breastmilk from patients undergoing sirolimus therapy do not exist and breastfeeding during study treatment is prohibited

Study Design

Enrollment

6 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (sirolimus)

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.

Interventions

Biospecimen Collection

Undergo collection of blood

Bone Marrow Aspiration

Undergo bone marrow biopsy/aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy/aspiration

Questionnaire Administration

Ancillary studies

Sirolimus

Given PO

Primary outcome measure

Incidence of grade 3+ treatment-related adverse events (TRAEs) [ Time Frame: From study day 1 (week 1) to 30 days after the last dose of sirolimus ]

Central Contacts and Locations

Central contacts

Anna Regina Samson

503-494-0793 samsonan@ohsu.edu

Locations

OHSU Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97239

Contacts

Anna Regina Samson

503-494-0793 samsonan@ohsu.edu

Principal Investigator:

Curtis A. Lachowiez

More Information

Sponsor

OHSU Knight Cancer Institute

Last update posted

Sep 28, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-29. This information was provided to ClinicalTrials.gov by OHSU Knight Cancer Institute on 2026-09-28. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.