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

NCT06261060 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2023-0918NCI-2024-01333
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Familial Platelet Disorder; Hematopoietic

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Arm 1

EXPERIMENTAL

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.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Given by PO

Arm 1

Eligibility Criteria

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

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney DiNardo, MD

CONTACT

(713) 794-1141; cdinardo@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 15, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): June 11, 2026
• Study Completion (Estimated): June 11, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)