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

Phase 2

• Conditions: Anemia, Aplastic
• Interventions: Drug: cyclophosphamide, fludarabine , thymoglobulin

• Registration Number: NCT00737685
• Lead Sponsor: The Korean Society of Pediatric Hematology Oncology

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.

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 Timeline

• Study Start: 2006-01
• Study First Submitted: 2008-08-18
• Study First Submitted QC: 2008-08-18
• Study First Posted: 2008-08-19
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-23
• Last Update Posted: 2012-03-26
• Primary Completion: 2012-08
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria

• and either marrow criterion.

• Peripheral blood

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

• Bone marrow

  1. Severe hypocellularity (< 25%)
  2. 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.

  1. Heart: a shortening fraction > 30%, ejection fraction > 45%.
  2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
  3. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fludarabine	cyclophosphamide, fludarabine , thymoglobulin	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of