Allo HSCT for High Risk Hemoglobinopathies

Phase 2

Recruiting

• Conditions: Graft Failure; Sickle Cell Disease; Hemoglobinopathies
• Interventions: Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Thymoglobulin; Biological: Cell Infusion; Drug: Fludarabine; Drug: Sirolimus; Drug: Busulfan; Drug: Tacrolimus; Drug: Thiotepa; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil

• Registration Number: NCT06872333
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-11-19
• Status Verified: 2025-03
• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-06
• Last Update Submitted: 2025-03-06
• Study First Posted: 2025-03-12
• Last Update Posted: 2025-03-12
• Primary Completion: 2030-06-01
• Study Completion: 2032-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

• Sickle Cell Disease (SCD)
• SCD Patients with a fully matched sibling donor (MSD) irrespective of the frequency or severity of symptoms MSD transplant can be considered. Parents/patient must be counseled as to the risks and benefits and provide their voluntary informed consent
• Transfusion Dependent Alpha- or Beta- Thalassemia
• Diamond Blackfan Anemia
• Other Non-Malignant Hematologic Disorders
• Karnofsky ≥ 60%, Lansky play score ≥ 60. Patients with lower performance score can be considered based on study team's evaluation.
• Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the transplant.

Exclusion Criteria

• Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment
• HIV Positive
• Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted
• Known allergy to any of the study components
• Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
• Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm D	Mycophenolate Mofetil	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm A	Alemtuzumab	Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI
Arm A	Total Body Irradiation	Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI
Arm A	Cell Infusion	Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI
Arm A	Sirolimus	Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI
Arm A	Mycophenolate Mofetil	Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI
Arm B	Cell Infusion	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm B	Thymoglobulin	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm B	Fludarabine	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm B	Busulfan	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm B	Tacrolimus	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm B	Mycophenolate Mofetil	Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu
Arm C	Cell Infusion	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm C	Thymoglobulin	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm C	Fludarabine	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm C	Busulfan	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm C	Tacrolimus	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm C	Mycophenolate Mofetil	Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu
Arm D	Total Body Irradiation	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Cell Infusion	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Thymoglobulin	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Fludarabine	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Thiotepa	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Cyclophosphamide	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI
Arm D	Sirolimus	Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI

Primary Outcome Measures

Name	Time	Method
Incidence of Graft versus Host Disease (GvHD)	1 year

Secondary Outcome Measures

Name	Time	Method
Overall Survival	1 and 2 years	Overall survival post HCT
Grade 3-4 Acute GvHD	2 years	Grade 3-4 acute Graft versus Host Disease (GvHD) at 2 years post HCT.
Chronic Graft versus Host Disease (GvHD) Free	2 years	Chronic Graft versus Host Disease (GvHD) Free at 2 years post HCT.
Failure Free Survival	2 years	Failure Free Survival 2 years post HCT.

Trial Locations

Locations (1)

Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States