NCT03653338

T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

T-Cell Depleted, Alternative Donor Transplant in Pediatric and Adult Patients With Severe Sickle Cell Disease (SCD) and Other Transfusion-Dependent Anemias

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Sponsor: Paul Szabolcs · Academic / Other
• Sex: All
• Age: 5 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.

Detailed description

CD3/CD19 depletion of mismatched donor grafts in the setting of reduced intensity, immune-ablative conditioning for patients with sickle cell disease and other transfusion-dependent anemias should sufficiently achieve engraftment while decreasing the incidence of treatment-related toxicities and achieving an acceptable incidence of graft versus host disease. Utilizing mismatched unrelated volunteer donors and haploidentical related donors will increase the number of patients able to undergo hematopoietic stem cell transplant (HSCT) for these diseases. Additionally, the institutional availability of virus-specific, donor-derived cytotoxic T lymphocytes should address complicated viral infections refractory to standard anti-viral therapy. The purpose is to: * To provide alternate donor transplantation from cryopreserved stem cell grafts that are fully characterized for safety and potency to patients with severe sickle cell disease, beta-thalassemia major, or Diamond-Blackfan anemia who do not have matched sibling donor, matched unrelated donor or cord blood donor options. * To utilize a reduced-intensity conditioning regimen to achieve minimal treatment-related morbidity and mortality while attaining sustained donor engraftment and donor chimerism \>20% in order to rescue disease phenotype, specifically in SCD patients. * To utilize ex-vivo T-cell depletion methods to prevent graft-versus-host disease in the setting of mismatched donor transplantation. * To utilize additional donor cell products to ensure sufficient immune reconstitution in the immediate post-transplant period, to improve mixed chimerism or provide non-specific anti-viral activity in patients with virus reactivation in the post-transplant period. * To utilize calcineurin inhibitor-free regimen in an effort to minimize/prevent central nervous system toxicity

Conditions

• Sickle Cell Anemia
• Beta-thalassemia Major
• Diamond-blackfan Anemia

Interventions

Type	Name	Description
BIOLOGICAL	CD3/CD19 depleted leukocytes	Negative selection for CD3+/CD19+ cells will be performed on the CliniMACS® depletion device.
BIOLOGICAL	CD45RA depleted leukocytes	Negative selection for CD45RA will be performed on the CliniMACS® depletion device.
DRUG	Hydroxyurea	Sickle Cell Disease Conditioning
DRUG	Rituximab	Sickle Cell Disease Conditioning
DRUG	Alemtuzumab	Sickle Cell Disease Conditioning
DRUG	Fludarabine	Sickle Cell Disease Conditioning
DRUG	Thiotepa	Sickle Cell Disease Conditioning

Timeline

• Start date: 2018-08-02
• Primary completion: 2026-08-01
• Completion: 2027-08-01
• First posted: 2018-08-31
• Last updated: 2025-08-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study