Clinical trial NCT00774527: Comparison of Cy-Atg Vs Cy-Flu-Atg for the Conditioning Therapy in Allo-HCT
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Marrow Failure Syndromes
Lead sponsor: Cooperative Study Group A for Hematology
Sponsor class: NETWORK
First posted: 2008-10-17
Enrollment: 82
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (FludaraÂ®, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of regimen related toxicities
timeFrame: 7 years
Secondary outcomes:
measure: Secondary end point will be the occurrence of engraftment failure (primary and secondary)
timeFrame: 7years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Kyoo-Hyung Lee, Doctor
role: PRINCIPAL_INVESTIGATOR
References: