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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Guangxi Medical University
Sponsor:
Information provided by (Responsible Party):
Lan YongRong, Guangxi Medical University
ClinicalTrials.gov Identifier:
NCT01766375
First received: December 28, 2012
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open, Randomized-control Study to Compare the Effects and Safety of Idarubicin-strengthened Pretreatment Program and Conventional Busulfan Cyclophosphamide Pretreatment Program on High-risk Acute Myeloid Leukemia Patient

Resource links provided by NLM:


Further study details as provided by Guangxi Medical University:

Primary Outcome Measures:
  • 2-year disease-free survival (DFS) rates [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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:
  • 2-year overall survival (OS) rates [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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


Other Outcome Measures:
  • safety of idarubicin 60mg/M2 combined with BUCY pretreatment program or BUCY pretreatment program [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    safety evaluation (early complications of transplantation, liver, kidney and heart toxicity, treatment-related mortality, blood recovery time),


Estimated Enrollment: 200
Study Start Date: August 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IDBUCY

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.

Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate
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.
Active Comparator: BUCY

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.

Drug: Cyclosporin A,mycophenolate mofetil,Methotrexate
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766375

Contacts
Contact: Lai Yongrong, doctor 0086-13517711828 laiyongrong@263.net
Contact: Li Qiaochuan, doctor 0086-13768411929 liqiaochuan@sohu.com

Locations
China, Guangxi
First Affiliated Hospital of Guangxi Medical University Recruiting
Nanning, Guangxi, China, 530021
Contact: Lai Yongrong, doctor    0086-13517711828    laiyongrong@263.net   
Contact: Zhang Zhongming, doctor    0086-15807801369    zzmmissyou@126.com   
Principal Investigator: Lai Yongrong, doctor         
Sub-Investigator: Zhang Zhongming, doctor         
Sub-Investigator: Li Qiaochuan, doctor         
Sponsors and Collaborators
Guangxi Medical University
  More Information

Additional Information:
No publications provided

Responsible Party: Lan YongRong, Director of the Hematology department of the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University
ClinicalTrials.gov Identifier: NCT01766375     History of Changes
Other Study ID Numbers: GuangXi-AML- HSCT-2012-07
Study First Received: December 28, 2012
Last Updated: January 9, 2013
Health Authority: China:The First Affiliated Hospital of Guangxi Medical University
China:Shanghai Ruijin Hospital
China:Guangdong Provincial People's Hospital
China:Wuhan Tongji Hospital
China:Yunnan Military Hospital
China:The First People's Hospital of Shanghai
China:The First Affiliated Hospital of Chongqing Medical University
China:Affiliated Hospital of Guiyang Medical College
China:The First Affiliated Hospital of Xinjiang Medical College
China:The First People's Hospital of Yunnan Province
China:The First Affiliated Hospital of Anhui Medical University
China:Tang Du Hospital of Fourth Military Medical University
China:The First Affiliated Hospital of Nanchang University
China:Henan Cancer Hospital

Keywords provided by Guangxi Medical University:
idarubicin
busulfan
cyclophosphamide
pretreatment
high-risk acute myeloid leukemia patient

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Mycophenolate mofetil
Idarubicin
Mycophenolic Acid
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014