Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia - Full Text View

Purpose

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

Condition	Intervention	Phase
Acquired Aplastic Anemia	Drug: Fludarabine Drug: Cyclophosphamide Biological: anti-thymocyte globulin Biological: filgrastim Radiation: Total body irradiation Procedure: CD3-depleted hematopoietic cell transplantation	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Anemia Aplastic Anemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

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 [ Time Frame: 2 years posttransplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To assess engraftment and graft failure [ Time Frame: 28 days posttransplant ] [ 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 posttransplant ] [ Designated as safety issue: Yes ]
Number of patients with acute GVHD.
To assess treatment related mortality [ Time Frame: 100 days posttransplant ] [ Designated as safety issue: Yes ]
Number of death after transplantation
To estimate overall survival and failure free survival [ Time Frame: 1 year posttransplant ] [ Designated as safety issue: No ]

Estimated Enrollment:	10
Study Start Date:	September 2012
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HAPLO	Drug: Fludarabine 40mg/M2 once daily IV on days -7 to -4 Drug: Cyclophosphamide 60 mg/kg IV on day-3 and -2 Biological: anti-thymocyte globulin Biological: filgrastim Other Name: Beginning on day 4 and continuing until blood counts recover Radiation: Total body irradiation 200 cGy per day on D-5 & -4 Procedure: CD3-depleted hematopoietic 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759732

Contacts

Contact: Ho Joon Im, MD, PhD

82-2-3010-3371

hojim@amc.seoul.kr

Locations

Korea, Republic of
Asan Medical Center	Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Ho Joon Im, MD, PhD 82-2-3010-3371 hojim@amc.seoul.kr
Sub-Investigator: Kyung Nam Koh, MD, PhD

Sponsors and Collaborators

Asan Medical Center

Investigators

Principal Investigator:

Ho Joon Im, MD, PhD

Asan Medical Center

More Information

Additional Information:

Aplastic anemia This link exits the ClinicalTrials.gov site

Anemia

Fludarabine This link exits the ClinicalTrials.gov site

Publications:

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. 2011 Nov 5; [Epub ahead of print] No abstract available.

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.

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.

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.

Responsible Party:	Ho Joon Im, Professor, Asan Medical Center
ClinicalTrials.gov Identifier:	NCT01759732 History of Changes
Other Study ID Numbers:	AMCPHO-SCT1202
Study First Received:	December 30, 2012
Last Updated:	December 30, 2012
Health Authority:	Korea: Institutional Review Board

Keywords provided by Asan Medical Center:

Aplastic anemia
T cell dose
CD3 depletion
Haploidentical hematopoietic stem cell transplantation

Additional relevant MeSH terms:

Anemia, Aplastic
Anemia
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Cyclophosphamide
Fludarabine monophosphate
Lenograstim
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 22, 2013