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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MST（microtransplantation）<br>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<br>* HLA mismatched donor G-CSF mobilized peripheral stem cell infused 24 hours (day 0) after the completion of chemotherapy<br>* Other names: microtransplantation;Drug: Ara-C<br>* 2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose<br>* Other names: conditioning reginmen;|
| Active Comparator: NST（nonmyeloablative transplantation）<br>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<br>* HLA matched donor G-CSF mobilized peripheral stem cell infused after the conditioning reginmen<br>* Other names: nonmyeloablative transplantation;Drug: cyclosporine A<br>* The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil<br>* Other names: GVHD prophylaxis;Drug: Mycophenolate mofetil<br>* The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil<br>* Other names: GVHD prophylaxis;Drug: Ara-C<br>* 2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose<br>* Other names: conditioning reginmen;Drug: fludarabine<br>* 30 mg/m2/d for 5days<br>* Other names: NST conditioning reginmen;Drug: anti-lymphocyte globulin<br>* 1.5-2 mg/kg/d for 4 days<br>* Other names: NST conditioning reginmen;Drug: cyclophosphamide<br>* 40 mg/kg/d for 2 days<br>* Other names: NST conditioning reginmen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-related mortality |  | 2 years | 
| donor chimerism or microchimerism |  | 10 years | 
| WT1+CD8+CTL | donor versus leukemia effect | 10 years | 
| GVHD |  | 10 years | 
| disease free survival |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, microtransplantationHLA-mismatched microtransplantation, nonmyeloablative stem cell transplantation, graft-versus-host disease