Comparison of Cy-Atg Vs Cy-Flu-Atg for the Conditioning Therapy in Allo-HCT

Bone Marrow Failure Syndromes Clinical Trial

— CyFluCyATG  

Official title:

Randomized Comparison of Cyclophosphamide Versus Cyclophosphamide Plus Fludarabine In Addition To Anti-Thymocyte Globulin for the Conditioning Therapy in Allogeneic Hematopoietic Cell Transplantation for Bone Marrow Failure Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00774527
• Other study ID #: C-002
• Status: Completed
• Phase: Phase 3
• First received: October 12, 2008
• Last updated: February 16, 2011
• Start date: March 2003
• Est. completion date: January 2011

Study information

• Verified date: February 2011
• Source: Cooperative Study Group A for Hematology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Randomized comparison of cyclophosphamide versus reduced-dose cyclophosphamide plus fludarabine in addition to anti-thymocyte globulin for the conditioning therapy in allogeneic hematopoietic cell transplantation for bone marrow failure syndrome.

Description:

This is a prospective, randomized, non-blind study.

Conditioning therapy will start on day -5 in patients who are randomized to receive Cy+ATG. Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Mesna 12 mg/kg iv push immediately before Cy and 3, 6, 9, and 12 hours after Cy. Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include methylprednisolone 2 mg/kg iv infusion, Tylenol 600 mg po, and Avil 45.5 mg iv push. The doses of cyclophosphamide and ATG (ALG) will be calculated using actual body weight.

Conditioning therapy will start on day -6 in patients who are randomized to receive Cy+fludarabine (Fludara®, Berlex Laboratories, Richmond, CA)+ATG. Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 5 consecutive days (days -6 to -2). Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include methylprednisolone 2 mg/kg iv infusion, Tylenol 600 mg po, and Avil 45.5 mg iv push. Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -3. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -3 to -2 by pump through a central venous catheter. Mesna 12 mg/kg iv push immediately before Cy and 3, 6, 9, and 12 hours after Cy. The doses of cyclophosphamide and ATG (ALG) will be calculated using actual body weight.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: January 2011
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with bone marrow failure syndrome.

• Written informed consent must be obtained from the patients and donors.

• Patients should have an HLA-identical or one-locus mismatched sibling, family or unrelated donor who is 60 years or less.

• Patients should be 15 years of age or older, but younger than 60 years.

• The performance status of the patients should be 70 or over by Karnofsky performance scale (see Appendix I).

• Patients should not have major illness or organ failure.

• Patients must have adequate hepatic function (bilirubin less than 2 mg/dl, AST and ALT less than three times the upper normal limit).

• Patients must have adequate renal function (creatinine less than 2.0 mg/dl).

• Patients must have adequate cardiac function (ejection fraction > 45% on MUGA scan).

• Patients must not have a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlikely, and making informed consent impossible.

• Patients must not be in pregnancy.

Exclusion Criteria:

• Patients should have major illness or organ failure

Study Design

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

Related Conditions & MeSH terms

• Bone Marrow Failure Syndromes
• Hemoglobinuria, Paroxysmal
• Pancytopenia

Intervention

Drug:
• Cyclophosphamide-fludarabine-anti thymocyte globulin
Cyclophosphamide 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 5 consecutive days (days -6 to -2). Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Cooperative Study Group A for Hematology

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of regimen related toxicities	1.1 Compare the regimen related toxicities of two different conditioning regimens, cyclophosphamide (Cy)+anti-thymocyte globulin (ATG) (Cy-ATG) vs. reduced dose of Cy+fludarabine (Flu)+ATG (Cy-Flu-ATG) after allogeneic hematopoietic cell transplantation (allo-HCT).	7 years	No
Secondary	Secondary end point will be the occurrence of engraftment failure (primary and secondary)		7years	No

External Links

•   Cy-ATG vs Cy-Flu-ATG