Collecting stem cells from patients with RUNX1 Familial Platelet Disorder

Protocol Title: Safety and Feasibility of Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis in Participants With RUNX1 Familial Platelet Disorder

This study is testing whether it's safe and possible to collect stem cells from people with RUNX1 Familial Platelet Disorder to help with future treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06414889 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and feasibility of collecting hematopoietic stem cells (HSCs) from participants diagnosed with RUNX1 Familial Platelet Disorder (RUNX1 FPD). The primary objective is to assess the safety of harvesting these stem cells, while secondary objectives focus on the feasibility of the collection process and gathering relevant data. Participants will receive treatments including G-CSF and Plerixafor to mobilize stem cells for apheresis. The study aims to provide insights into the potential for future therapies using these stem cells.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 12 to 75 with a confirmed diagnosis of RUNX1 FPD.

Not a fit: Patients with conditions that disqualify them from undergoing apheresis or those with uncontrolled blood pressure may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could pave the way for new treatment options for patients with RUNX1 Familial Platelet Disorder.

How similar studies have performed: Other studies involving stem cell mobilization have shown promise, but this specific approach in RUNX1 FPD is novel.

Eligibility criteria

Inclusion Criteria:

Participants who meet all of the following criteria are eligible to be included in the study:

1. Are aged ≥ 18 to 75 years

   a. Once a favorable review of safety has been completed by the SMC in 3 participants aged ≥ 18 years, the study will be opened to participants aged ≥ 12 years.
2. Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative \[LAR\]), as described in Appendix 1, Section 13.1
3. Have a confirmed diagnosis of RUNX1 FPD, verified by a Clinical Laboratory Improvement Amendments (CLIA)-certified genetic sequencing report.
4. Clearance by apheresis team to proceed
5. Have systolic blood pressure ≤ 170 mm Hg and diastolic blood pressure ≤ 95 mmHg
6. Are eligible for HSCT per institution requirements
7. Have a Lansky (age \< 16 years)/Karnofsky performance status of ≥ 70 (see Appendix 2, Section 13.2).
8. Are willing and able to comply with protocol-defined contraceptive requirements (see Appendix 3 Section 13.3)
9. Have a platelet count ≥ 50,000/μL for initiation of apheresis, assessed within 24 hours prior to the procedure, or, if \< 50,000/μL are administered platelets on the day of the collection

   a. If the apheresis team decides that a central venous catheter (CVC) is to be placed, platelet count should be ≥ 50,000 prior to catheter placement.
10. Have hemoglobin ≥ 7.5 g/dL as assessed within 24 hours prior to the procedure

Exclusion Criteria:

Participants who meet any of the following criteria are excluded from the study:

1. Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
2. Have uncontrolled bleeding
3. Are using supplemental oxygen
4. Have known severe splenomegaly (≥ 20 cm)
5. Have a diagnosis of MDS or hematologic malignancies, as defined by WHO hematolymphoid tumor classification fifth edition (Khourey et al 2022) hematolymphoid tumor classification fifth edition (Khourey et al 2022)
6. Have recent prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ Note: Cancer treated with curative intent \< 5 years previously may be allowed following approval from the study investigator. Cancer treated with curative intent \> 5 years previously is allowed.
7. Have any prior or current myeloproliferative or a significant coagulation or immunodeficiency disorder
8. Have advanced liver disease, defined as any of the following:

   1. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value \> 5× the upper limit of normal (ULN) at screening
   2. Screening prothrombin time (PT) or partial thromboplastin time (PTT) \> 1.5× ULN
9. Have had prior HSCT or gene therapy
10. Have history of concomitant sickle cell disease
11. Have been treated with an investigational drug within 30 days of screening or 5 half-lives (whichever is longer)
12. Have a positive test result for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) at screening

    1. Participants with positive hepatitis B core antibody (HbcAb) and/or hepatitis B-e antibody (HbeAb) are eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR).
    2. Participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR.
13. Have a positive infectious disease panel at screening for human T-lymphotropic virus 1 or 2 (HTLV-1 and HTLV-2), or syphilis (rapid plasma 24 reagin \[RPR\])
14. Have clinically significant and active bacterial, viral, fungal, or parasitic infection at screening
15. Have a white blood cell (WBC) count \< 2 × 109/L
16. Have a left ventricular ejection fraction \< 45%
17. Have a screening estimated glomerular filtration rate \< 60 mL/min/1.73 m2
18. Have a diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study
19. For women of childbearing potential: are pregnant or breastfeeding or lack adequate contraception
20. Are unable to comply with the study procedures, as assessed by the investigator

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Chitra Hosing — M.D. Anderson Cancer Center
• Study coordinator: Chitra Hosing, MD

Conditions RUNX1 Familial Platelet Disorder