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

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

Sponsors

Lead Sponsor: Asan Medical Center

Source Asan Medical Center
Brief 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.

Overall Status Completed
Start Date July 2009
Completion Date July 2012
Primary Completion Date July 2012
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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
Secondary Outcome
Measure Time Frame
To assess engraftment and graft failure 28 days post-transplant
To estimate the risk of acute GVHD 100 days post-transplant
To assess treatment related mortality 100 days post-transplant
To estimate overall survival 1 year after transplantation
Enrollment 12
Condition
Intervention

Intervention Type: Biological

Intervention Name: anti-thymocyte globulin

Description: On days -3 to -1

Arm Group Label: HAPLO

Intervention Type: Biological

Intervention Name: filgrastim

Description: Beginning on day 4 and continuing until blood counts recover

Arm Group Label: HAPLO

Intervention Type: Drug

Intervention Name: Fludarabine

Description: 30mg/M2 once daily IV on days -6 to -2

Arm Group Label: HAPLO

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: 60 mg/kg IV on day-3 and -2

Arm Group Label: HAPLO

Intervention Type: Procedure

Intervention Name: CD3±CD19 depleted hematopoietic stem cell transplantation

Description: Immunogenetic depletion on CliniMACS

Arm Group Label: HAPLO

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

Gender: All

Minimum Age: N/A

Maximum Age: 21 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ho Joon Im, MD & PhD Principal Investigator Asan Medical Center
Location
Facility: Asan Medical Center
Location Countries

Korea, Republic of

Verification Date

December 2012

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Asan Medical Center

Investigator Full Name: Ho Joon Im

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: HAPLO

Type: Experimental

Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov