HLA-mismatched MST vs HLA-matched NST for AML in Intermediate-risk

Sponsor

The Affiliated Hospital of the Chinese Academy of Military Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT02461121

Collaborator

(none)

156

Enrollment

Location

Arms

108

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with de novo AML enrolled in the study. Patient who has a HLA-identical donor is assigned to receive NST therapy with GVHD prophylaxis and who has no HLA-identical donor is assigned to receive MST therapy without GVHD prophylaxis.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Genetic: HLA mismatched stem cell Genetic: HLA matched stem cell Drug: cyclosporine A Drug: Mycophenolate mofetil Drug: Ara-C Drug: fludarabine Drug: anti-lymphocyte globulin Drug: cyclophosphamide	Phase 3

Detailed Description

The optimal therapy for intermediate-risk patients with acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Recent studies shown that microtransplantation (MST) can improve survival in AML-CR1 patients. However, a comparison study between the MST and nonmyeloablative stem cell transplantation (NST) is lacking. 156 intermediate-risk AML-CR1 patients aged 9 to 59 years were enrolled in this study. Patients with de novo AML enrolled in the study. Patient who has a HLA-identical donor is assigned to receive NST therapy with GVHD prophylaxis and who has no HLA-identical donor is assigned to receive MST therapy without GVHD prophylaxis.

Study Design

Study Type:

Interventional

Actual Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Compare the Safety and Effective of HLA-mismatched Microtransplantation With HLA-matched Nonmyeloablative Transplantation for Acute Myeloid Leukemia in Intermediate-risk

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MST（microtransplantation） The microtransplantation conditioning regimen included high-dose Ara-C chemotherapy (2.0 to 2.5 g/m2 per 12 hours intravenously on days -4 to -2) followed by an infusion of HLA mismatched stem cell 24 hours (day 0) after the completion of cytarabine.	Genetic: HLA mismatched stem cell HLA mismatched donor G-CSF mobilized peripheral stem cell infused 24 hours (day 0) after the completion of chemotherapy Other Names: microtransplantation Drug: Ara-C 2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose Other Names: conditioning reginmen
Active Comparator: NST（nonmyeloablative transplantation） The NST（nonmyeloablative transplantation）conditioning regimen consisted of 30 mg/m2/d fludarabine for days -6 to -2, 1.5-2 mg/kg/d anti-lymphocyte globulin for days -5 to -2, 40 mg/kg/d cyclophosphamide for days -4 and -2 and 2.0-3.0 g/m2/d cytarabine for days -6 to -4，followed by an infusion of HLA matched stem cell after the completion of regimen. The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil	Genetic: HLA matched stem cell HLA matched donor G-CSF mobilized peripheral stem cell infused after the conditioning reginmen Other Names: nonmyeloablative transplantation Drug: cyclosporine A The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil Other Names: GVHD prophylaxis Drug: Mycophenolate mofetil The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil Other Names: GVHD prophylaxis Drug: Ara-C 2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose Other Names: conditioning reginmen Drug: fludarabine 30 mg/m2/d for 5days Other Names: NST conditioning reginmen Drug: anti-lymphocyte globulin 1.5-2 mg/kg/d for 4 days Other Names: NST conditioning reginmen Drug: cyclophosphamide 40 mg/kg/d for 2 days Other Names: NST conditioning reginmen

Arm

Intervention/Treatment

Experimental: MST（microtransplantation）

The microtransplantation conditioning regimen included high-dose Ara-C chemotherapy (2.0 to 2.5 g/m2 per 12 hours intravenously on days -4 to -2) followed by an infusion of HLA mismatched stem cell 24 hours (day 0) after the completion of cytarabine.

Genetic: HLA mismatched stem cell

HLA mismatched donor G-CSF mobilized peripheral stem cell infused 24 hours (day 0) after the completion of chemotherapy

Other Names:

microtransplantation

Drug: Ara-C

2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose

Other Names:

conditioning reginmen

Active Comparator: NST（nonmyeloablative transplantation）

The NST（nonmyeloablative transplantation）conditioning regimen consisted of 30 mg/m2/d fludarabine for days -6 to -2, 1.5-2 mg/kg/d anti-lymphocyte globulin for days -5 to -2, 40 mg/kg/d cyclophosphamide for days -4 and -2 and 2.0-3.0 g/m2/d cytarabine for days -6 to -4，followed by an infusion of HLA matched stem cell after the completion of regimen. The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Genetic: HLA matched stem cell

HLA matched donor G-CSF mobilized peripheral stem cell infused after the conditioning reginmen

Other Names:

nonmyeloablative transplantation

Drug: cyclosporine A

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Other Names:

GVHD prophylaxis

Drug: Mycophenolate mofetil

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Other Names:

GVHD prophylaxis

Drug: Ara-C

2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose

Other Names:

conditioning reginmen

Drug: fludarabine

30 mg/m2/d for 5days

Other Names:

NST conditioning reginmen

Drug: anti-lymphocyte globulin

1.5-2 mg/kg/d for 4 days

Other Names:

NST conditioning reginmen

Drug: cyclophosphamide

40 mg/kg/d for 2 days

Other Names:

NST conditioning reginmen

Outcome Measures

Primary Outcome Measures

Overall Survival [10 years]

Secondary Outcome Measures

treatment-related mortality [2 years]
donor chimerism or microchimerism [10 years]
WT1+CD8+CTL [10 years]
donor versus leukemia effect
GVHD [10 years]
disease free survival [10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

9 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have elderly (9-59 ages) AML pathologically confirmed per WHO guidelines.
Patients WITH intermediate-risk AML-CR1
Patients must have ECOG Performance status of 0,1,or 2. If ECOG 2.
Patients must have a HLA mismatched donor who should be able to provide informed consent.
All genders and races are eligible.
ALT and AST≤3 ×ULN, TBIL≤1.5 × ULN, Cr≤2 ×ULN or CrCl≥40 mL/min
By means of ultrasonic Heartbeat map or multiple gated acquisition (MUGA) scanning determination of LVEF in the normal range.
Donors must be able to safely undergo leukapheresis.

Exclusion Criteria:

received operation 4 weeks before randomization
acute promyelocytic leukemia,Myeloid sarcoma, chronic myeloid leukemia in accelerated phase and blastic phase;
active CNS disease, pregnancy, or other major medical or psychiatric illnesses that could compromise tolerance to this protocol
Require the use of warfarin or equivalent of vitamin K antagonists (such as phenprocoumon) anticoagulant.
There is clinical significance of cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months before randomization, or any heart function grade 3 (moderate) or 4 (severe ) heart disease in accordance with the functional classification method of New York Heart Association (NYHA).
Known to have the following history: human immunodeficiency virus (HIV) or active hepatitis C virus or hepatitis B virus infection
Any situation processed by the PI that will be damaged to the patients safety.
Patients and / or authorized family member refuse to sign the consent. attend other clinical researchers in 3 months.
Donors exclusion criteria include:active infection or malignancy, cardiovascular instability, severe anemia, severe coagulation disorder, pregnancy, inadequate venous access, inability to provide consent, or any other condition deemed unsafe by the treatment staff.