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Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia

Primary Purpose

Acquired Aplastic Anemia

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
anti-thymocyte globulin
filgrastim
Total body irradiation
CD3-depleted hematopoietic cell transplantation
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acquired Aplastic Anemia focused on measuring Aplastic anemia, T cell dose, CD3 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 CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HAPLO

Arm Description

Outcomes

Primary Outcome Measures

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

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 and failure free survival

Full Information

First Posted
December 30, 2012
Last Updated
December 30, 2012
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01759732
Brief Title
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

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
December 2014 (Anticipated)
Study Completion Date
December 2015 (Anticipated)

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: 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

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HAPLO
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
40mg/M2 once daily IV on days -7 to -4
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
60 mg/kg IV on day-3 and -2
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
Beginning on day 4 and continuing until blood counts recover
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation
Intervention Description
200 cGy per day on D-5 & -4
Intervention Type
Procedure
Intervention Name(s)
CD3-depleted hematopoietic cell transplantation
Intervention Description
Immunogenetic depletion on CliniMACS
Primary Outcome Measure Information:
Title
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
Time Frame
2 years posttransplant
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 posttransplant
Title
To estimate the risk of acute GVHD
Description
Number of patients with acute GVHD.
Time Frame
100 days posttransplant
Title
To assess treatment related mortality
Description
Number of death after transplantation
Time Frame
100 days posttransplant
Title
To estimate overall survival and failure free survival
Time Frame
1 year posttransplant

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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ho Joon Im, MD, PhD
Phone
82-2-3010-3371
Email
hojim@amc.seoul.kr
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
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ho Joon Im, MD, PhD
Phone
82-2-3010-3371
Email
hojim@amc.seoul.kr
First Name & Middle Initial & Last Name & Degree
Kyung Nam Koh, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
22533862
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.
Results Reference
background
PubMed Identifier
22546497
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.
Results Reference
background
PubMed Identifier
22635243
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.
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&...
Description
Fludarabine
URL
http://druginfo.nlm.nih.gov/drugportal/ProxyServlet
Description
Cyclophosphamide

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Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia

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