search
Back to results

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

Primary Purpose

Aplastic Anemia

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
Fludarabine
Cyclophosphamide
CD3±CD19 depleted hematopoietic stem cell transplantation
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring Aplastic anemia, Fludarabine, CD3±CD19 depletion, Haploidentical hematopoietic stem cell transplantation

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HAPLO

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To assess engraftment and graft failure
Number of patients who failed to engraft by 28 days.
To estimate the risk of acute GVHD
Number of patients with acute GVHD.
To assess treatment related mortality
Number of death after transplantation
To estimate overall survival

Full Information

First Posted
April 8, 2010
Last Updated
December 30, 2012
Sponsor
Asan Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT01105273
Brief Title
Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia
Keywords
Aplastic anemia, Fludarabine, CD3±CD19 depletion, Haploidentical hematopoietic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HAPLO
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Description
On days -3 to -1
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
Beginning on day 4 and continuing until blood counts recover
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
30mg/M2 once daily IV on days -6 to -2
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
60 mg/kg IV on day-3 and -2
Intervention Type
Procedure
Intervention Name(s)
CD3±CD19 depleted hematopoietic stem cell transplantation
Intervention Description
Immunogenetic depletion on CliniMACS
Primary Outcome Measure Information:
Title
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.
Time Frame
2 years post-transplant
Secondary Outcome Measure Information:
Title
To assess engraftment and graft failure
Description
Number of patients who failed to engraft by 28 days.
Time Frame
28 days post-transplant
Title
To estimate the risk of acute GVHD
Description
Number of patients with acute GVHD.
Time Frame
100 days post-transplant
Title
To assess treatment related mortality
Description
Number of death after transplantation
Time Frame
100 days post-transplant
Title
To estimate overall survival
Time Frame
1 year after transplantation

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ho Joon Im, MD & PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
14676782
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. doi: 10.1038/sj.bmt.1704358.
Results Reference
background
PubMed Identifier
11244448
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. doi: 10.1038/sj.bmt.1702748.
Results Reference
background
PubMed Identifier
15846294
Citation
Lacerda JF, Martins C, Carmo JA, Lourenco 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. doi: 10.1016/j.bbmt.2005.02.007. No abstract available.
Results Reference
background
PubMed Identifier
20040760
Citation
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.
Results Reference
background
PubMed Identifier
22055111
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.
Results Reference
result
PubMed Identifier
25310303
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.
Results Reference
derived
Links:
URL
http://www.nlm.nih.gov/medlineplus/anemia.html
Description
Anemia
URL
http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=021679141&QV1=FLUDARABINE
Description
Fludarabine
URL
http://druginfo.nlm.nih.gov/drugportal/ProxyServlet
Description
Cyclophosphamide

Learn more about this trial

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

We'll reach out to this number within 24 hrs