Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia

Aplastic Anemia Clinical Trial

Official title:

HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3±CD19 Depletion for Patients With Aplastic Anemia After Conditioning of Fludarabine, Cyclophosphamide and Antithymocyte Globulin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01105273
• Other study ID #: AMCPHO-SCT0802
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 8, 2010
• Last updated: December 30, 2012
• Start date: July 2009
• Est. completion date: July 2012

Study information

• Verified date: December 2012
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Rationale: Chemotherapy with fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion CD3±CD19 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.

Purpose: This phase I/II trial is to evaluate the safety and efficacy of fludarabine, cyclophosphamide and antithymocyte globulin with CD3±CD19 depleted graft from haploidentical donors in treating patients with aplastic anemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• 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

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Biological:
• anti-thymocyte globulin
On days -3 to -1
• filgrastim
Beginning on day 4 and continuing until blood counts recover

Drug:
• Fludarabine
30mg/M2 once daily IV on days -6 to -2
• Cyclophosphamide
60 mg/kg IV on day-3 and -2

Procedure:
• CD3±CD19 depleted hematopoietic stem 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 (5)

Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V; Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010 Apr 29;115(17):3437-46. doi: 10.1182/blood-2009-03-207001. Epub 2009 Dec 29. — 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

Kremens B, Basu O, Grosse-Wilde H, Sauerwein W, Schaefer UW, Havers W. Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia. Bone Marrow Transplant. 2001 Jan;27(1):111-3. — View Citation

Lacerda JF, Martins C, Carmo JA, Lourenço F, Juncal C, Ismail S, Lacerda JM. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant. 2005 May;11(5):399-400. — View Citation

Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horwitz E, Houston J, Kasow K, Leung W, Wang W, Yusuf U, Handgretinger R. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant. 2004 Feb;33(4):411-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the engraftment rate and survival of CD3±CD19 depleted haploidentical peripheral blood stem cell transplantation after conditioning with fludarabine, cyclophosphamide and anti-thymocyte globulin.		2 years post-transplant	Yes
Secondary	To assess engraftment and graft failure	Number of patients who failed to engraft by 28 days.	28 days post-transplant	Yes
Secondary	To estimate the risk of acute GVHD	Number of patients with acute GVHD.	100 days post-transplant	Yes
Secondary	To assess treatment related mortality	Number of death after transplantation	100 days post-transplant	Yes
Secondary	To estimate overall survival		1 year after transplantation	No

External Links

•   Anemia
•   Fludarabine