Clinical trial NCT01759732: Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia
Official title: Haploidentical Stem Cell Transplantation With Fixed Dose of T Cells After in Vitro T Cell Depletion Using CD3 Monoclonal Antibody for Children With Acquired Severe Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acquired Aplastic Anemia
Keywords: Aplastic anemia
T cell dose
CD3 depletion
Haploidentical hematopoietic stem cell transplantation
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2013-01-03
Enrollment: 10
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: Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion of CD3 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.

Purpose: Phase II trials to evaluate the efficacy of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia


Eligibility criteria: Inclusion Criteria:

* Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:

  * Granulocyte count \< 500/mm3,
  * Corrected reticulocyte count \< 1%,
  * Platelet count \< 20,000/mm3
* No HLA-identical family member or closely matched (8 of 8 HLA-locus match) unrelated marrow donor available
* HLA-haploidentical related donor available

Exclusion Criteria:

* Paroxysmal nocturnal hemoglobinuria or Fanconi anemia
* Clonal cytogenetic abnormalities or myelodysplastic syndromes
* Active fungal infections
* HIV positive
* Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
* Pregnant or nursing

Primary outcomes:
measure: To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia
timeFrame: 2 years 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 assess treatment related mortality
timeFrame: 100 days posttransplant
measure: To estimate overall survival and failure 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: Burroughs LM, Woolfrey AE, Storer BE, Deeg HJ, Flowers ME, Martin PJ, Carpenter PA, Doney K, Appelbaum FR, Sanders JE, Storb R. Success of allogeneic marrow transplantation for children with severe aplastic anaemia. Br J Haematol. 2012 Jul;158(1):120-8. doi: 10.1111/j.1365-2141.2012.09130.x. Epub 2012 Apr 26.
citation: Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty JM, Adams RH, Ewell M, Leifer ES, Gersten ID, Carter SL, Horowitz MM, Nakamura R, Pulsipher MA, Difronzo NL, Confer DL, Eapen M, Anderlini P. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biol Blood Marrow Transplant. 2012 Jul;18(7):1007-11. doi: 10.1016/j.bbmt.2012.04.014. Epub 2012 Apr 27.
citation: Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant. 2012 Dec;47(12):1507-12. doi: 10.1038/bmt.2012.79. Epub 2012 May 28.
citation: Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. No abstract available.
citation: Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients. Bone Marrow Transplant. 2015 Feb;50(2):225-31. doi: 10.1038/bmt.2014.232. Epub 2014 Oct 13.