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

NCT ID: NCT06261060

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-20
• Study Completion Date: 2028-06-11

Brief Summary

To learn about the safety and effects of low-dose sirolimus in participants with RUNX1-FPD.

Detailed Description

Primary Objective:

• Evaluate the safety and tolerability of low-dose sirolimus in participants with RUNX1 familial platelet disorder (RUNX1-FPD)

Secondary Objectives:

• Evaluate increases in platelet counts during and after treatment with low-dose sirolimus
• Evaluate changes in somatic mutation variant allele frequency (VAF)
• Monitor the rate of somatic mutation acquisition (ie, mutation burden)
• Assess change in platelet aggregation score
• Measure the change from baseline in bleeding score (ISTH-BAT)
• Evaluate change in mTORC1 downstream signaling (pS6/EBP)

Exploratory Objectives:

• Measure rescue of elevated cytokine profiles
• Evaluate reversal of myeloid skewing using flow cytometry
• Determine changes in bone marrow (eg, megakaryocytic atypia and cellularity)
• Assess changes in patient-reported outcomes measures (eg, EORTC and PRO-CTCAE)
• Describe the pharmacokinetics of sirolimus in patients with RUNX1-FPD
• Determine the correlation between sirolimus trough levels and each endpoint

Conditions

Familial Platelet Disorder; Hematopoietic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Participants will visit the study clinic 2 times during Week 1, one (1) time during Weeks 2-4, and then 1 time every 2 weeks after that (Weeks 6, 8, 10, and so on) until Week 22 (Month 6). Then participants will have a follow-up visit at Week 24 and again at Week 52 (Month 12). Participants will take sirolimus by mouth every day, at about the same time each day. Swallow the tablet(s) whole with a full glass of water (about 1 cup). Do not crush or chew the tablet(s). Participants may take sirolimus with or without food.

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Given by PO

Interventions

Sirolimus

Given by PO

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants has provided signed, informed consent before initiation of any study specific procedures
• Aged ≥18 years at the time of signing the informed consent
• Confirmed P/LP germline RUNX1 variant per ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) RUNX1-specific variant curation rules80
• Participants must be willing to provide bone marrow sample at time of screening and at the end of treatment with sirolimus
• Platelet count of ≥50,000/µL
• Adequate renal function: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation, >30 mL/min/1.73m2
• Adequate hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × upper limit of normal (ULN) and total bilirubin <1.5 × ULN
• Adequate cardiac function: left ventricular ejection fraction >50%

Exclusion Criteria

• Known allergy to sirolimus
• History of lymphoma or other hematologic malignancies
• Uncontrolled bleeding
• Any prior diagnosis of myelodysplastic syndrome 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; eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, and clarithromycin), strong inducers of CYP3A4 (eg, rifampin and rifabutin), other drugs that could increase sirolimus blood concentrations (eg, bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors [eg, ritonavir, indinavir, boceprevir, and telaprevir], metoclopramide, nicardipine, troleandomycin, and verapamil), other drugs that could decrease sirolimus blood concentrations (eg, carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort [Hypericum perforatum]), or drugs with blood concentrations that could increase (eg, verapamil) within 7 days before study day 1
• Use of cannabidiol, which can increase blood levels of sirolimus, within 7 days before study day 1
• 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 (eg, 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 (eg, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid) within 28 days before study day 1
• Known diagnosis of chronic viral infection (eg, hepatitis B or C or HIV, and Epstein-Barr) or tuberculosis
• Women who are pregnant, may become pregnant, or who are breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Courtney DiNardo, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Courtney DiNardo, MD

Role: CONTACT

cdinardo@mdanderson.org

(713) 794-1141

Facility Contacts

Courtney DiNardo, MD

Role: primary

cdinardo@mdanderson.org

713-794-1141

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2024-01333

Identifier Type: OTHER

Identifier Source: secondary_id

2023-0918

Identifier Type: -

Identifier Source: org_study_id