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

October 7, 2026 updated by: Curtis Lachowiez, OHSU Knight Cancer Institute

Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder - Part II

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate the safety and tolerability of low-dose sirolimus in patients with RUNX1 familial platelet disorder (RUNX1-FPD).

SECONDARY OBJECTIVES:

I. Evaluate platelet counts. II. Evaluate changes in somatic mutation variant allele frequency (VAF). III. Evaluate somatic mutation acquisition (i.e., mutation burden). IV. Evaluate the change in platelet function. V. Evaluate the change from baseline in bleeding score (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool [ISTH-BAT]).

VI. Evaluate the change in mTORC1 downstream signaling.

EXPLORATORY OBJECTIVES:

I. Evaluate the rescue of elevated cytokine profiles. II. Evaluate the reversal of myeloid skewing using colony formation assay. III. Evaluate monocytes using clinical flow cytometry. IV. Evaluate changes in patient-reported quality of life (QoL) outcomes measures (e.g., Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events [PRO-CTCAE]).

V. Determine the pharmacokinetics of sirolimus in participants with RUNX1-FPD. VI. Evaluate the correlation between sirolimus trough levels and each endpoint. VII. Make bone marrow smears and bone marrow biopsy slides. VIII. Evaluate the cellularity of bone marrow after study treatment.

OUTLINE:

Patients receive sirolimus orally (PO) once daily (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.

After completion of study treatment, patients are followed for 6 months.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Knight Cancer Institute Clinical Trials Information
  • Phone Number: 503-494-1080
  • Email: trials@ohsu.edu

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • OHSU Knight Cancer Institute
        • Principal Investigator:
          • Curtis A. Lachowiez
        • Contact:
          • Knight Cancer Institute Clinical Trials Information
          • Phone Number: 503-494-1080
          • Email: trials@ohsu.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Other: Questionnaire Administration

Ancillary studies

Procedure: Biospecimen Collection

Undergo collection of blood

Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Bone Marrow Aspiration

Undergo bone marrow biopsy/aspiration

Procedure: Bone Marrow Biopsy

Undergo bone marrow biopsy/aspiration

Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Drug: Sirolimus

Given PO

Other Names:
  • Rapamycin
  • Rapamune
  • AY 22989
  • RAPA
  • SILA 9268A
  • WY-090217
  • AY-22989
  • AY22989
  • SILA-9268A
  • SILA9268A
  • WY 090217
  • WY090217

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in platelet count
Time Frame: From screening, pre dose on study day 1 (week 1) to end of treatment (EOT) (week 24, day 168)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
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
Time Frame: From screening to end of study (EOS) (week 52, day 365)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
From screening to end of study (EOS) (week 52, day 365)
Change in number of clonal hematopoiesis of indeterminate potential mutations
Time Frame: From screening to EOS (week 52, day 365)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
From screening to EOS (week 52, day 365)
Change in percent positivity based on activated GPIIb IIIa and surface P selectin and CD42b
Time Frame: From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
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)
Time Frame: From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)
Change in the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool score
Time Frame: From study day 1 (week 1) to EOS (week 52, day 365)

Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
From study day 1 (week 1) to EOS (week 52, day 365)
Change in the relative amount of the protein 4eBP1
Time Frame: From screening, pre dose on study day 1 (week 1) to EOS (week 52, day 365)

Will be based on flow cytometry and immunohistochemistry assays. Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.
From screening, pre dose on study day 1 (week 1) to EOS (week 52, day 365)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
OHSU Knight Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Oregon Health and Science University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Curtis A Lachowiez, OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 5, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00028610
  • P30CA069533 (U.S. NIH Grant/Contract)
  • NCI-2026-03902 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • STUDY00028610 (Other Identifier: OHSU Knight Cancer Institute)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings