Using low-dose sirolimus to improve blood function in patients with a genetic platelet disorder
Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder
This study is testing whether a low dose of sirolimus can help improve blood function in people with a genetic platelet disorder called RUNX1 familial platelet disorder.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 6 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | M.D. Anderson Cancer Center Academic / other |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT06261060 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and tolerability of low-dose sirolimus in patients diagnosed with RUNX1 familial platelet disorder (RUNX1-FPD). The study will assess various outcomes, including changes in platelet counts, somatic mutation burden, and patient-reported outcomes. Participants will undergo treatment with sirolimus and will be monitored for changes in their hematopoietic function and overall health. The trial includes both primary and exploratory objectives to gather comprehensive data on the drug's effects.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed RUNX1 genetic variant and a platelet count of at least 50,000/µL.
Not a fit: Patients with a history of lymphoma or other hematologic malignancies, or those with known allergies to sirolimus, may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve platelet function and reduce bleeding risks for patients with RUNX1-FPD.
How similar studies have performed: While this approach is novel for RUNX1-FPD, similar studies using sirolimus in other hematological conditions have shown promising results.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Houston, Texas
- MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Courtney DiNardo, MD — M.D. Anderson Cancer Center
- Study coordinator: Courtney DiNardo, MD
- Email: cdinardo@mdanderson.org
- Phone: (713) 794-1141
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.