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

NCT01105273 | Completed Phase 1

• 1 other identifier: AMCPHO-SCT0802
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Aplastic Anemia

Keywords

Aplastic anemia; Fludarabine; CD3±CD19 depletion; Haploidentical hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (1)

HAPLO

EXPERIMENTAL

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: CD3±CD19 depleted hematopoietic stem cell transplantation

Interventions

anti-thymocyte globulin BIOLOGICAL

On days -3 to -1

HAPLO

filgrastim BIOLOGICAL

Beginning on day 4 and continuing until blood counts recover

HAPLO

Fludarabine DRUG

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

HAPLO

Cyclophosphamide DRUG

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

HAPLO

CD3±CD19 depleted hematopoietic stem cell transplantation PROCEDURE

Immunogenetic depletion on CliniMACS

HAPLO

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (6)

• 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.

  PMID: 14676782 BACKGROUND

• 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.

  PMID: 11244448 BACKGROUND

• 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.

  PMID: 15846294 BACKGROUND

• 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.

  PMID: 20040760 BACKGROUND

• 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.

  PMID: 22055111 RESULT

• 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.

  PMID: 25310303 DERIVED

Related Links

• Anemia
• Fludarabine
• Cyclophosphamide

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Antilymphocyte Serum; Filgrastim; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Ho Joon Im, MD & PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 16, 2010
• Study Start: July 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: January 3, 2013

Record last verified: 2012-12

Locations

KR (1)