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

Aplastic Anemia Clinical Trial

Official title:

Reduced Toxicity Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00882323
• Other study ID #: KSPHO-SCT 0802
• Status: Recruiting
• Phase: Phase 2
• First received: April 15, 2009
• Last updated: March 23, 2012
• Start date: November 2008
• Est. completion date: October 2012

Study information

• Verified date: March 2012
• Source: The Korean Society of Pediatric Hematology Oncology
• Contact: Hyoung Jin Kang, M.D, Ph.D
• Phone: 82 2 2072 3304
• Email: kanghj[@]snu.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Cyclophosphamide, Fludarabine, Thymoglobulin
cyclophosphamide (60 mg/kg once daily i.v. on days -8, -7) fludarabine (40 mg/m2 once daily i.v. on days -6, -5, -4, -3, -2) thymoglobulin (2.5 mg/kg once daily i.v. on days -4, -3, -2)

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
The Korean Society of Pediatric Hematology Oncology

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA.		From Nov. 2008 to Oct. 2012	No
Secondary	To evaluate overall and EFS rate after UBMT/PBSCT.		From Nov. 2008 to Oct. 2012	No
Secondary	To evaluate GVHD and immunologic recovery after UBMT/PBSCT.		From Nov. 2008 to Oct. 2012	No