Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia

Acquired Aplastic Anemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01759732
• Other study ID #: AMCPHO-SCT1202
• Status: Recruiting
• Phase: Phase 2
• First received: December 30, 2012
• Last updated: December 30, 2012
• Start date: September 2012
• Est. completion date: December 2015

Study information

• Verified date: December 2012
• Source: Asan Medical Center
• Contact: Ho Joon Im, MD, PhD
• Phone: 82-2-3010-3371
• Email: hojim[@]amc.seoul.kr
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Aplastic Anemia
• Anemia
• Anemia, Aplastic

Intervention

Drug:
• Fludarabine
40mg/M2 once daily IV on days -7 to -4
• Cyclophosphamide
60 mg/kg IV on day-3 and -2

Biological:
• anti-thymocyte globulin

• filgrastim

Radiation:
• Total body irradiation
200 cGy per day on D-5 & -4

Procedure:
• CD3-depleted hematopoietic cell transplantation
Immunogenetic depletion on CliniMACS

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

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. — View 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 ap — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 years posttransplant	Yes
Secondary	To assess engraftment and graft failure	Number of patients who failed to engraft by 28 days	28 days posttransplant	Yes
Secondary	To estimate the risk of acute GVHD	Number of patients with acute GVHD.	100 days posttransplant	Yes
Secondary	To assess treatment related mortality	Number of death after transplantation	100 days posttransplant	Yes
Secondary	To estimate overall survival and failure free survival		1 year posttransplant	No

External Links

•   Anemia