A Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Severe Aplastic Anemia Patients With COH-MC-17: A Non-Myeloablative/ Reduced-Intensity, Conditioning Regimen and CD4+ T-Cell-Depleted Haploidentical Hematopoietic Transplant
City of Hope Medical Center
Summary
This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid. It may also lower the body's immune response. Pentostatin blocks a protein needed for cell growth. Anti-thymocyte globulin is an immunosuppressive drug can destroy immune cells known as T-cells. HaploHCT transfers blood-forming stem cells from a healthy partially-matched donor to a patient. Administering a regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin before haploHCT may help make room for the new, healthy cells and may reduce the risk of graft versus host disease.
Description
PRIMARY OBJECTIVES: I. To determine if the infusion of CD4+ T-cell-depleted hematopoietic cells from a haploidentical donor, following a non-myeloablative/ reduced-intensity preparative regimen is safe in patients with severe aplastic anemia (SAA). II. To determine the feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product, as assessed by: IIa. Ability to meet the minimum required CD34+ cell dose, and; IIb. Ability to meet the CD4+ T-cell depletion product release requirements. SECONDARY OBJECTIVES: I. To evaluate toxicities including type, frequency, severi…
Eligibility
- Age range
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * RECIPIENT: Documented informed consent of the participant. * RECIPIENT: Age: \>= 40 years but =\< 75 years of age at time of enrollment. * RECIPIENT: Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenia and fulfillment of SAA disease criteria at least 3 months after initial IST) or having relapsed (initial improvement of cytopenia after first-line IST but then a later return to fulfillment of SAA disease criteria when IST is decreased or ceased). IST could have included anti-thymocyte globulin (ATG) based regim…
Interventions
- BiologicalAnti-Thymocyte Globulin
Given IV
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspirate
Undergo bone marrow aspirate
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- DrugCyclophosphamide
Given PO and IV
- ProcedureHaploidentical Hematopoietic Cell Transplantation
Undergo CD4+ T-cell depleted haploHCT
- DrugPentostatin
Location
- City of Hope Medical CenterDuarte, California