Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia

• Sponsor: Asan Medical Center (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT01759732
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.3

Study Details

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

Condition or Disease	Intervention/Treatment	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 Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Sep 1, 2012
• Anticipated Primary Completion Date: Dec 1, 2014
• Anticipated Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

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 Names: 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

Outcome Measures

Primary Outcome Measures

1. 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 [2 years posttransplant]

Secondary Outcome Measures

1. To assess engraftment and graft failure [28 days posttransplant]

   Number of patients who failed to engraft by 28 days

2. To estimate the risk of acute GVHD [100 days posttransplant]

   Number of patients with acute GVHD.

3. To assess treatment related mortality [100 days posttransplant]

   Number of death after transplantation

4. To estimate overall survival and failure free survival [1 year posttransplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Anemia

Publications

• 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
• Other Study ID Numbers: AMCPHO-SCT1202
• First Posted: Jan 3, 2013
• Last Update Posted: Jan 3, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by Ho Joon Im, Professor, Asan Medical Center: Aplastic anemia; T cell dose; CD3 depletion; Haploidentical hematopoietic stem cell transplantation
• Additional relevant MeSH terms: Anemia; Anemia, Aplastic; Cyclophosphamide; Fludarabine; Antilymphocyte Serum

Study Results

No Results Posted as of Jan 3, 2013