Haploidentical Hematopoietic Stem Cell Transplantation, Malignant Disease, Non-malignant Disease
Conditions
Keywords
Children and adolescents, Malignant disease, Non-malignant disease, TCRαβ depletion, Haploidentical hematopoietic stem cell transplantation
Brief summary
Purpose of study: This phase I/II trial is to evaluate the safety and feasibility of TCRαβ-depleted graft from haploidentical family donors in treating children and adolescents with malignant or non-malignant diseases.
Interventions
BIOLOGICALfilgrastim
Beginning on day 4 and continuing until blood counts recover
RADIATIONTotal body irradiation
200 cGy per day on D-6 to -4 (eligible disease except aplastic anemia) 200 cGy per day on D-5 & -4 (severe aplastic anemia)
PROCEDURETCRαβ-depleted hematopoietic cell transplantation
DEVICECliniMACS
Immunogenetic depletion of TCRαβ cells
DRUGFludarabine
40mg/M2 once daily IV on days -7 to -2
DRUGCyclophosphamide
50 mg/kg IV on day -3 and -2
BIOLOGICALanti-thymocyte globulin
Sponsors
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
A. Disease inclusions 1. Hematologic malignancy: * Acute lymphoblastic leukemia including induction failure, CR1 (Ph+, t(4:11), hypodiploid and other very high risk features), ≥ CR2, infant ALL with MLL or other unfavorable features * Acute myeloid leukemia excluding CR1 with t(8:21), inv(16), t(15:17), and Down syndrome * Myelodysplastic syndrome: RCC with -7 or RCC in need of transfusion * Chronic myeloid leukemia in AP * Juvenile myelomonocytic leukemia * Malignant lymphoma, NHL or HD, after failed autologous HSCT * Other 2. Non-hematologic malignancy * Relapsed or refractory solid tumors including neuroblastoma, rhabdomyosarcoma and so on 3. Non-malignant hematologic disease * Acquired severe and very severe aplastic anemia * Fanconi anemia * Paroxysmal nocturnal hemoglobinuria * Congenital dyserythropoietic anemia * Others 4. Inherited or metabolic disease * Hemophagocytic lymphohistiocytosis * Malignant osteopetrosis * Storage diseases * Others B. Recipient inclusions 1\. Age \< 21 years 2. No HLA-identical stem cell donor available 3. Lansky-Play performance score \>60 4. No active infection at the time of transplantation
Exclusion criteria
1. HIV-infection 2. Presence of active and serious infection 3. Cardiac ejection fraction \<35% on echocardiography 4. Severe pulmonary dysfunction (DLCO \<30%) 5. Liver function abnormalities with bilirubin \>4mg/dL and elevation of transaminases \> 400U/L 6. Concurrent severe or uncontrolled medical disease 7. Patients who are pregnant 8. Patients unwilling or unable to comply with the protocol or unable to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRαβ-depleted graft | 1 year posttransplant |
Secondary
| Measure | Time frame |
|---|---|
| To assess engraftment and graft failure | 28 days posttransplant |
| To estimate the risk of acute GVHD | 100 days posttransplant |
| To estimate the incidence of relapse | 100 days and 1 year post-transplant |
| To estimate the incidence and severity of chronic GVHD | 1 year posttransplant |
| To estimate the overall survival | 1 year posttransplant |
| To estimate the incidence of bacterial, fungal and viral infection | 100 days and 1 year posttransplant |
| To estimate the reactivation rate of CMV, EBV | 100 days and 1 year posttransplant |
| To evaluate the immune reconstitution of T, B, and NK cells | days 7, 14, 21, 28, 60, 90, 180, 270, and 365 days post-transplant |
| To evaluate the lineage-specific chimerism using flow cytomery of CD3+, CD19, CD56, TCR αβ, and TCRγδ at pre-transplant | days 7, 10, 14, 21, 28, 60, 90, 180, 270 and 365 post-transplant |
| To assess event free survival | 1 year posttransplant |
Countries
South Korea
Contacts
Primary ContactHo Joon Im, MD, PhD
Outcome results
None listed