NCT06872333

Allo HSCT for High Risk Hemoglobinopathies

Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 55 Years
• Healthy volunteers: Accepted

Summary

A single center, open label, interventional, phase II trial for donor transplant for high risk hemoglobinopathies and other red cell transfusion dependent disorders utilizing allogeneic hematopoietic stem cell transplantation (HSCT) regimens.

Conditions

• Graft Failure
• Sickle Cell Disease
• Hemoglobinopathies

Interventions

Type	Name	Description
DRUG	Alemtuzumab	Alemtuzumab (Campath) will be administered IV over 2 hours on day -8 to day -4.
RADIATION	Total Body Irradiation	400 cGy in 2 split fractions will be administered per Department of RadiationOncology SOPs.
BIOLOGICAL	Cell Infusion	On day 0 the cells will be infused per cell source specific institutional guidelines
DRUG	Thymoglobulin	ATG will be administered IV every 24 hours beginning on day -8 for all patients. Dosing will be model-based using Bayesian methodology13,14,15. Total doses and total number of doses (1-4 doses) will be determined based on absolute lymphocyte count and weight.
DRUG	Fludarabine	Fludarabine will be administered IV over 1 hour every 24 hours on day -5 to day - 2. The daily dose of fludarabine will be determined by model-based dosing utilizing Bayesian methodology with a cumulative area under the curve (cAUC) of 20 mg\*hr/L (range 18-22 mg\*hr/L).
DRUG	Busulfan	Busulfan dosing and administration and therapeutic drug monitoring (TDM) per institutional guidelines. Initial busulfan dosing will be determined by model-based dosing utilizing Bayesian methods with a cumulative area under the curve (cAUC) of 75 mg\*hr/L.
DRUG	Thiotepa	Thiotepa will be administered at a dose 5 mg/kg IV every 12 hours on day - 7 over 2 hours. Patients will undergo thiotepa skin care per institutional guidelines
DRUG	Cyclophosphamide	Cyclophosphamide will be administered at a dose of 14.5 mg/kg over 2 hours IV daily on days -6 and -5. Cyclophosphamide dosing is calculated based on actual body weight (ABW). For Arm D - Cyclophosphamide 50 mg/kg IV will be administered over 2 hours on days +3 and +4. Cyclophosphamide dosing for post-transplant is calculated based on ideal body weight (IBW) unless patient weighs less than IBW, in which case actual body weight (ABW) will be used.
DRUG	Sirolimus	Patients on Arm A and Arm D will receive sirolimus; beginning on day -3 and continuing until day +180 for patients on Arm A or beginning on day +5 and continuing until 1 year post transplant for patients on Arm D.
DRUG	Tacrolimus	Patients on Arm B and Arm C will receive tacrolimus, beginning on day -3 and continuing until day +180. Tacrolimus dosing and monitoring will be per institutional guidelines.
DRUG	Mycophenolate Mofetil	MMF will begin on day -3 (Arm A, B \& C) or day +5 (Arm D). Patients treated on adult service will receive 15 mg/kg (max 1500 mg/dose) given every 12 hours, rounded to nearest 250 mg. Patients on pediatric service will receive 15 mg/kg (max 1000 mg/dose) given every 8 hours. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. MMF will be stopped at day +30 (Arms A, B \& C) or day +35 (Arm D) or 7 days after engraftment, whichever day is later, if no acute GVHD.

Timeline

• Start date: 2024-11-19
• Primary completion: 2030-06-01
• Completion: 2032-06-01
• First posted: 2025-03-12
• Last updated: 2026-03-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study