Clinical trial NCT02014506: Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents
Official title: Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Haploidentical Hematopoietic Stem Cell Transplantation
Malignant Disease
Non-malignant Disease
Keywords: Children and adolescents
Malignant disease
Non-malignant disease
TCRαβ depletion
Haploidentical hematopoietic stem cell transplantation
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2013-12-18
Enrollment: 30
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: To evaluate tralsplant-related mortality after haploidentical hematopoietic stem cell transplantation using TCRαβ-depleted graft
timeFrame: 1 year posttransplant
Secondary outcomes:
measure: To assess engraftment and graft failure
timeFrame: 28 days posttransplant
measure: To estimate the risk of acute GVHD
timeFrame: 100 days posttransplant
measure: To estimate the incidence of relapse
timeFrame: 100 days and 1 year post-transplant
measure: To estimate the incidence and severity of chronic GVHD
timeFrame: 1 year posttransplant
measure: To estimate the overall survival
timeFrame: 1 year posttransplant
measure: To estimate the incidence of bacterial, fungal and viral infection
timeFrame: 100 days and 1 year posttransplant
measure: To estimate the reactivation rate of CMV, EBV
timeFrame: 100 days and 1 year posttransplant
measure: To evaluate the immune reconstitution of T, B, and NK cells
timeFrame: days 7, 14, 21, 28, 60, 90, 180, 270, and 365 days post-transplant
measure: To evaluate the lineage-specific chimerism using flow cytomery of CD3+, CD19, CD56, TCR αβ, and TCRγδ at pre-transplant
timeFrame: days 7, 10, 14, 21, 28, 60, 90, 180, 270 and 365 post-transplant
measure: To assess event free survival
timeFrame: 1 year posttransplant
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Ho Joon Im, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.