Flu+CPM+rATG Conditioning Regimes for Unrelated Bone Marrow Transplantation (UBMT)(or Mobilized Peripheral Blood)in Severe Aplastic Anemia (SAA)

Sponsor

The Korean Society of Pediatric Hematology Oncology (Other)

Overall Status

Unknown status

CT.gov ID

NCT00737685

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Anti-thymocyte globulin (ATG) has been used in severe aplastic anemia as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine based conditioning regimens without total body irradiation have been reported to be promising for BMT/PBSCT from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in UBMT/UPBSCT.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Aplastic	Drug: cyclophosphamide, fludarabine , thymoglobulin	Phase 2

Detailed Description

GVHD prophylaxis recommendation tacrolimus (0.03 mg/kg/day i.v. by continuous infusion from day -2 and taper with an oral form until 1 year after BMT/PBSCT) methotrexate (15 mg/m2 i.v. on days 1 and 10 mg/m2 i.v. on days 3, 6, 11)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Bone Marrow (or Mobilized Peripheral Blood) Transplantation in Severe Aplastic Anemia

Study Start Date :

Jan 1, 2006

Anticipated Primary Completion Date :

Aug 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fludarabine	Drug: cyclophosphamide, fludarabine , thymoglobulin cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 & -6) fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 & -2) thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 & -1)

Arm

Intervention/Treatment

Experimental: Fludarabine

Drug: cyclophosphamide, fludarabine , thymoglobulin

cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 & -6) fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 & -2) thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 & -1)

Outcome Measures

Primary Outcome Measures

To evaluate the engraftment potential, incidence and severity of acute graft versus host disease,toxicity of conditioning regimen for UBMT in SAA. [From Jan. 1. 2006 to Dec. 31. 2008. For 3 years.]
To evaluate overall and EFS follow-up of 1 year after UBMT/PBSCT. [From Jan. 1. 2006 to Dec. 31. 2008. For 3 years]

Secondary Outcome Measures

To evaluate chronic GVHD and immunologic recovery after UBMT/PBSCT. and the efficacy of UBMT/PBSCT before immuno-suppressive therapy with anti-thymocyte globulin in severe aplastic anemia and long term toxicity of non-TBI based conditioning [From Jan. 1. 2006 to Dec. 31. 2008. For 3 years.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria
and either marrow criterion.
Peripheral blood

Neutrophils < 0.5 x 109/l
Platelets < 20 x 109/l
Corrected reticulocytes < 1%

Bone marrow

Severe hypocellularity (< 25%)
Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells

No prior hematopoietic stem cell transplantation.
Age: no limits.
Performance status: ECOG 0-2.
Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases.

Heart: a shortening fraction > 30%, ejection fraction > 45%.
Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.

Patients must lack any active viral infections or active fungal infection.
Appropriate donor is available: Matched in 6/6 of A, B, DR loci.
Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria:

Pregnant or nursing women.
Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
Psychiatric disorder that would preclude compliance.
Congenital aplastic anemia including Fanconi anemia.
Manipulated bone marrow.