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

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Marrow Failure Syndromes
• Intervention / Treatment: Drug: Cyclophosphamide-fludarabine-anti thymocyte globulin

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 Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

No Intervention: ArmI(CyATG); •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

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.; Other Names: CYCLOPHOSPHAMIDE,FLUDARA,ANTI-THYMOCYTE GLOBULINE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary end point will be the occurrence of engraftment failure (primary and secondary)	7years

Collaborators and Investigators

• Sponsor: Cooperative Study Group A for Hematology
• Investigators: Principal Investigator: Kyoo-Hyung Lee, Doctor, Asan Medical Center

Publications and helpful links

Helpful Links

• Cy-ATG vs Cy-Flu-ATG

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 12, 2008
• First Submitted That Met QC Criteria: October 16, 2008
• First Posted (Estimate): October 17, 2008

Study Record Updates

• Last Update Posted (Estimate): February 17, 2011
• Last Update Submitted That Met QC Criteria: February 16, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Bone Marrow Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Myelodysplastic Syndromes; Syndrome; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinuria, Paroxysmal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Antilymphocyte Serum
• Other Study ID Numbers: C-002