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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ho Joon Im, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01105273
First received: April 8, 2010
Last updated: December 30, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Aplastic Anemia
Biological: anti-thymocyte globulin
Biological: filgrastim
Drug: Fludarabine
Drug: Cyclophosphamide
Procedure: CD3±CD19 depleted hematopoietic stem cell transplantation
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

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. [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess engraftment and graft failure [ Time Frame: 28 days post-transplant ] [ Designated as safety issue: Yes ]
    Number of patients who failed to engraft by 28 days.

  • To estimate the risk of acute GVHD [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
    Number of patients with acute GVHD.

  • To assess treatment related mortality [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
    Number of death after transplantation

  • To estimate overall survival [ Time Frame: 1 year after transplantation ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: July 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HAPLO Biological: anti-thymocyte globulin
On days -3 to -1
Biological: filgrastim
Beginning on day 4 and continuing until blood counts recover
Drug: Fludarabine
30mg/M2 once daily IV on days -6 to -2
Drug: Cyclophosphamide
60 mg/kg IV on day-3 and -2
Procedure: CD3±CD19 depleted hematopoietic stem cell transplantation
Immunogenetic depletion on CliniMACS

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01105273

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Ho Joon Im, MD & PhD Asan Medical Center
  More Information

Additional Information:
Anemia  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: Ho Joon Im, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01105273     History of Changes
Other Study ID Numbers: AMCPHO-SCT0802
Study First Received: April 8, 2010
Last Updated: December 30, 2012
Health Authority: Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
Aplastic anemia
Fludarabine
CD3±CD19 depletion
Haploidentical hematopoietic stem cell transplantation

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Bone Marrow Diseases
Hematologic Diseases
Antilymphocyte Serum
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014