About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Biospecimen Collection
Procedure/Surgery
Undergo collection of blood
Bone Marrow Aspiration
Procedure/Surgery
Undergo bone marrow biopsy/aspiration
Bone Marrow Biopsy
Procedure/Surgery
Undergo bone marrow biopsy/aspiration
Questionnaire Administration
Other intervention
Ancillary studies
Sirolimus
Drug
Given PO

Treatment groups

6 Participants

are divided into 1 treatment group

Group A: Treatment (sirolimus)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Incidence of grade 3+ treatment-related adverse events (TRAEs)

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.

Time frame

From study day 1 (week 1) to 30 days after the last dose of sirolimus

Secondary outcomes

1

Change in platelet count

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.

Time frame

From screening, pre dose on study day 1 (week 1) to end of treatment (EOT) (week 24, day 168)

2

Change in variant allele frequency for existing clones

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.

Time frame

From screening to end of study (EOS) (week 52, day 365)

3

Change in number of clonal hematopoiesis of indeterminate potential mutations

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.

Time frame

From screening to EOS (week 52, day 365)

4

Change in percent positivity based on activated GPIIb IIIa and surface P selectin and CD42b

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.

Time frame

From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)

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

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts