the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient

Phase 3

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate

• Registration Number: NCT01766375
• Lead Sponsor: Guangxi Medical University

Brief Summary

This study was a multi-center, open, randomized-control study on the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on the overall survival rate and disease-free survival rate of acute myeloid leukemia patient in high-risk group over a period of 2 years.

Detailed Description

This study was a multi-center, open, randomized-control study. It evaluates the effects and safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group.

Patients enrolled were randomly divided into group A (idarubicin 60mg/M2 combined with BUCY group) and group B (BUCY group). SAS randomization software was used to obtain randomization numbers. Patients were recommend to start pretreatment within 7 days after randomization.

Main objective: 2-year overall survival (OS) and disease-free survival (DFS) rates.

Secondary objective: safety evaluation (early complications of transplantation, liver, kidney and heart toxicity, treatment-related mortality, blood recovery time), the median period of disease-free survival.

Test drugs Idarubicin (Zavedos ®, Pfizer), busulfan, cyclophosphamide.

Pretreatment plan Drug Group A (IDA 60mg/M2 + BUCY) Group B (BUCY) IDA: 20mg/m2 a day, d-12 \~d-10, intravenous infusion for 1 hour. BU: 4mg/Kg a day, oral administration, d-7 \~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7\~d-4.

CY: 60mg/Kg a day, intravenous infusion, d-3\~d-2. GVHD prevention plan GVHD is prevented by CSA+MMF+MTX in sibling allogeneic hematopoietic stem cell transplantation (starting from day -1, 3mg/kg of CSA was infused by continuous intravenous drip until gastrointestinal function returned normal when method of administration was changed to oral administration. 5mg/kg was divided into twice oral intakes, maintaining cyclosporine concentration at 200-300ug / L; MTX 15mg/m2 at day +1, 10mg/m2 at day +3, +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.25g BID starting from day 0 and continued for a month ). Unrelated allogeneic hematopoietic stem cell transplantation used CSA MMF MTX ATG for the prevention of GVHD. 3mg/kg CSA was infused through continuous intravenous drip since day -1 until gastrointestinal function returned to normal when the administration method was changed to oral. 5mg/kg was divided to twice oral intakes maintaining cyclosporine concentrations at 200-300ug/L; MTX 15mg/m2, at day +1, 10mg/m2 at day +3, day +6 and day +11 (based on actual situations day 11 can be omitted); MMF 0.5g BID starting from day 0 and continued for 3 months (a month later, dose can be reduced according to the hemogram); the total ATG was 6mg/kg and was taken in three days, from day -4 to day -2.

Relapse intervention Routine preventive DLI is not recommended, however, if tendency of recurrence found during monitor, chemotherapy, immunotherapy, targeted therapy, secondary transplantation, etc. can be used, and intervention treatment start time should be recorded as the end time.

The efficacy evaluation time point

1. 1-3, 6, 12, 18, 24 months after transplantation.

2. Follow-up evaluation: indicators such as blood routines and bone marrow detection, and minimal residual disease detection after the end of treatment should be done regularly.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-12-28
• Status Verified: 2013-01
• Study First Submitted QC: 2013-01-09
• Last Update Submitted: 2013-01-09
• Study First Posted: 2013-01-11
• Last Update Posted: 2013-01-11
• Primary Completion: 2016-01
• Study Completion: 2016-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Age: 18～50;
2. Received peripheral blood hematopoietic stem cell transplantation from siblings or unrelated allogeneic donors with identical matching of HLA or 1 alleles mismatched.
3. Diagnosis: refer to 2011 edition of AML China Guideline for the diagnosis and treatment and diagnosis standards of high-risk acute myeloid leukemia developed through literatures (see Appendix B);
4. Under general condition, ECOG score ≤ 1;
5. Normal cardiac functions;
6. Normal liver and renal function: blood bilirubin≤35 μ mol\/L, AST/ALT lower than twice in the upper limit of normal value, serum creatinine≤ 150 μ mol\/L;
7. Subjects have signed the informed consent form.

Exclusion Criteria

1. Severe uncontrolled infection before transplantation;
2. With contraindications of idarubicin;
3. Reached the maximum cumulative dose of anthracyclines, for instance, DNR≥ 450mg/m2, mitoxantrone≥140mg/m2, the total cumulative dose of idarubicin≥ 300mg/m2;
4. The other conditions that do not meet the inclusion criteria.

Withdrawal criteria:

1. Those do not meet the inclusion criteria or meet the exclusion criteria after reviewing;
2. Patient withdraws the informed consent form;
3. Patient violates the clinical study protocol;
4. Patient experiences severe adverse events that treatment has to be terminated;
5. Patient that considered no longer fit to complete clinical trials by researchers.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BUCY	Cyclosporin A,mycophenolate mofetil,Methotrexate	Busulfan: 4mg/Kg a day, oral administration, d-7 \~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7\~d-4. Cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3\~d-2.
IDBUCY	Cyclosporin A,mycophenolate mofetil,Methotrexate	Idarubicin: 20mg/m2 a day, d-12 \~d-10, intravenous infusion for 1 hour. Busulfan: 4mg/Kg a day, oral administration, d-7 \~d-4, or 3.2mg/Kg a day, intravenous infusion, d-7\~d-4. cyclophosphamide: 60mg/Kg a day, intravenous infusion, d-3\~d-2.

Primary Outcome Measures

Name	Time	Method
2-year disease-free survival (DFS) rates	4 years	The purpose of this study is to evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group.

Secondary Outcome Measures

Name	Time	Method
2-year overall survival (OS) rates	4 years	It evaluates the effects of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program on acute myeloid leukemia patient in high-risk group. 200 patients were studied with 100 patients in each group

Trial Locations

Locations (1)

First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China