Safety and Efficacy Study of Microtransplantation to Treat Elderly Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Patients enrolled from each center according to confirmed criteria specified in cooperative scheme are randomly assigned to standard induction and consolidation chemotherapy with microtransplantation （MST-group）or without (CT-group).Compare the remission rate and 2-year disease-free survival (DFS) and overall survival(OS) rate of the two groups.

Detailed Description
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Microtransplantation, which combines chemotherapy with adoptive infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC). Data from more than 70 elderly AML patients who received microtransplantation in Beijing showed that the remission rate and 2-year disease-free survival (DFS) reach 75-82% and 32-39% respectively, and microchimerisms (donor cells<1%) were detected without GVHD. The results have been clinically validated in several other centers in China, United States and Australia. Based on these facts, to further validate the therapeutic efficacy, we propose a phase III clinical trial in which the de novo AML patients ≥60 years old are randomly assigned to receive standard induction and consolidation chemotherapy with or without microtransplantation.

Official Title
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Phase III Clinical Trial of Microtransplantation to Treat Elderly Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Procedure: microtransplantation
* Biological: HLA-mismatched donor peripheral stem cell infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have elderly (60-85 ages) AML pathologically confirmed per WHO guidelines. Patients have not been treated before. 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 occurred stroke or intracranial hemorrhage within 6 months before randomization. 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: 60 Years
Maximum Age: 85 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: CT-group<br>standard induction and consolidation chemotherapy only, without microtransplantation | |
| Experimental: MST-group<br>standard induction and consolidation chemotherapy with microtransplantation | Procedure: microtransplantation<br>* infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC)<br>* Other names: DSI;Biological: HLA-mismatched donor peripheral stem cell infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the remission rate | ①bone marrow: blasts <5% (with a count of at least 200 Nucleated cells).②Hemogram: absolute neutrophil count of more than 1.0×109/L，platelets of >100×109/L. ③Clinical: Without the signs and symptoms caused by leukemia infiltration d , and independent of transfusion; | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | Measured from complete remission to the date of death or the date of last follow-up examination; | 2 years | 
| Overall Survival | measured from the Date of beginning therapy to the date of death or the date of last follow-up examination; | 2 YEAR | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donor, Acute Myeloid Leukemia, microtransplantation, elderly patients, HLA-mismatched, Peripheral, stem cell, infusion