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

Phase 3

Completed

• Conditions: Bone Marrow Failure Syndromes
• Interventions: Drug: Cyclophosphamide-fludarabine-anti thymocyte globulin

• Registration Number: NCT00774527
• Lead Sponsor: Cooperative Study Group A for Hematology

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2003-03
• Study First Submitted: 2008-10-12
• Study First Submitted QC: 2008-10-16
• Study First Posted: 2008-10-17
• Primary Completion: 2010-02
• Study Completion: 2011-01
• Status Verified: 2011-02
• Last Update Submitted: 2011-02-16
• Last Update Posted: 2011-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ArmI(CyATG)	Cyclophosphamide-fludarabine-anti thymocyte globulin	•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

Primary Outcome Measures

Name	Time	Method
Occurrence of regimen related toxicities	7 years	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).

Secondary Outcome Measures

Name	Time	Method
Secondary end point will be the occurrence of engraftment failure (primary and secondary)	7years

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of