Allo HSCT for High Risk Hemoglobinopathies

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 2

Conditions: Graft Failure; Hemoglobinopathies; Sickle Cell Disease

Treatments: Drug: Cyclophosphamide; Drug: Sirolimus; Drug: Fludarabine; Drug: Mycophenolate Mofetil; Biological: Cell Infusion; Drug: Thymoglobulin; Radiation: Total Body Irradiation; Drug: Thiotepa; Drug: Tacrolimus; Drug: Busulfan; Drug: Alemtuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06872333

2024LS140

Details and patient eligibility

About

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.

Enrollment: 62 estimated patients

Sex: All

Ages: Under 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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62 participants in 4 patient groups

Arm A

Experimental group

Description:

Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI

Treatment:

Drug: Alemtuzumab

Radiation: Total Body Irradiation

Biological: Cell Infusion

Drug: Mycophenolate Mofetil

Drug: Sirolimus

Arm B

Experimental group

Description:

Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu

Treatment:

Drug: Busulfan

Drug: Tacrolimus

Drug: Thymoglobulin

Biological: Cell Infusion

Drug: Mycophenolate Mofetil

Drug: Fludarabine

Arm C

Experimental group

Description:

Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu

Treatment:

Drug: Busulfan

Drug: Tacrolimus

Drug: Thymoglobulin

Biological: Cell Infusion

Drug: Mycophenolate Mofetil

Drug: Fludarabine

Arm D

Experimental group

Description:

Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI

Treatment:

Drug: Thiotepa

Radiation: Total Body Irradiation

Drug: Thymoglobulin

Biological: Cell Infusion

Drug: Mycophenolate Mofetil

Drug: Fludarabine

Drug: Sirolimus

Drug: Cyclophosphamide