Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)

Phase 2

• Conditions: Aplastic Anemia
• Interventions: Drug: Cyclophosphamide, Fludarabine, Thymoglobulin

• Registration Number: NCT00882323
• 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 graft versus host disease (GVHD) and rejection of organ transplants. As the fludarabine based conditioning regimens without total body irradiation have been reported to be promising for transplantation from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated donor transplantation. Our previous phase II study of fludarabine, cyclophosphamide plus thymoglobulin conditioning resulted in good engraftment (100%) and survival rate (74%). But grade III/IV toxicities occurred in 25% of patients and all events were treatment related mortalities. As cyclophosphamide is more toxic agent than fludarabine, we plan a new phase II study re; 'reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated donor transplantation in severe aplastic anemia' by reducing dosage of cyclophosphamide and increasing dosage of fludarabine.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2009-04-15
• Study First Submitted QC: 2009-04-15
• Study First Posted: 2009-04-16
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-23
• Last Update Posted: 2012-03-26
• Primary Completion: 2012-10
• Study Completion: 2012-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. 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

2. No prior hematopoietic stem cell transplantation.

3. Age: no limits.

4. Performance status: ECOG 0-2.

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

6. Patients must lack any active viral infections or active fungal infection.

7. Appropriate donor is available: Matched in 6/6 of A, B, DR loci.

8. Patients (or one of parents if patients age < 19) should sign informed consent.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fludarabine	Cyclophosphamide, Fludarabine, Thymoglobulin	-

Primary Outcome Measures

Name	Time	Method
To evaluate engraftment potential of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.	From Nov. 2008 to Oct. 2012

Secondary Outcome Measures

Name	Time	Method
To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA.	From Nov. 2008 to Oct. 2012
To evaluate overall and EFS rate after UBMT/PBSCT.	From Nov. 2008 to Oct. 2012
To evaluate GVHD and immunologic recovery after UBMT/PBSCT.	From Nov. 2008 to Oct. 2012

Trial Locations

Locations (1)

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