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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HAPLO | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine | Drug | 40mg/M2 once daily IV on days -7 to -2 |
| |
| Cyclophosphamide |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRαβ-depleted graft | 1 year posttransplant |
| Measure | Description | 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 |
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Inclusion Criteria:
A. Disease inclusions
Hematologic malignancy:
Non-hematologic malignancy
Non-malignant hematologic disease
Inherited or metabolic disease
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ho Joon Im, MD, PhD | Contact | 82-2-3010-3371 | hojim@amc.seoul.kr |
| Name | Affiliation | Role |
|---|---|---|
| Ho Joon Im, MD, PhD | Asan Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Recruiting | Seoul | 138-736 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24141651 | Background | Park JA, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ, Im HJ. Successful rescue of early graft failure in pediatric patients using T-cell-depleted haploidentical hematopoietic SCT. Bone Marrow Transplant. 2014 Feb;49(2):270-5. doi: 10.1038/bmt.2013.163. Epub 2013 Oct 21. | |
| 23380343 | Background | Im HJ, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, Chi HS, Seo JJ. Excellent outcome of haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia. Biol Blood Marrow Transplant. 2013 May;19(5):754-9. doi: 10.1016/j.bbmt.2013.01.023. Epub 2013 Feb 1. |
| Label | URL |
|---|---|
| fludarabine | View source |
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| Drug |
50 mg/kg IV on day -3 and -2 |
|
| anti-thymocyte globulin | Biological |
|
| filgrastim | Biological | Beginning on day 4 and continuing until blood counts recover |
|
| Total body irradiation | Radiation | 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) |
|
| TCRαβ-depleted hematopoietic cell transplantation | Procedure |
|
| CliniMACS | Device | Immunogenetic depletion of TCRαβ cells |
|
| 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 |
| 23993299 | Background | Schumm M, Lang P, Bethge W, Faul C, Feuchtinger T, Pfeiffer M, Vogel W, Huppert V, Handgretinger R. Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device. Cytotherapy. 2013 Oct;15(10):1253-8. doi: 10.1016/j.jcyt.2013.05.014. |
| cyclophosphamide | View source |
| leukemia | View source |
| ID | Term |
|---|---|
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| D000961 | Antilymphocyte Serum |
| D000069585 | Filgrastim |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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