Acute Myeloid Leukemia
Conditions
Keywords
Acute Myeloid Leukemia, microtransplantation, elderly patients, HLA-mismatched, donor, Peripheral, stem cell, infusion
Brief summary
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
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.
Interventions
PROCEDUREmicrotransplantation
infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC)
BIOLOGICALHLA-mismatched donor peripheral stem cell infusion
Sponsors
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the remission rate | 2 months | 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; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | 2 years | Measured from complete remission to the date of death or the date of last follow-up examination; |
| Overall Survival | 2 YEAR | measured from the Date of beginning therapy to the date of death or the date of last follow-up examination; |
Other
| Measure | Time frame | Description |
|---|---|---|
| treatment-related mortality | 2 years | Early mortality: death within 4 weeks after initiation of induction therapy |
| recipient versus leukemia effect | 2 YEAR | Analysis of recipient WT1 positive CD8 T cells by flow cytometry |
| donor chimerism or microchimerism | at count recovery prior to each new cycle of therapy, at 4 weeks after the last round of consolidation, and if still positive, every 3 months after completing therapy for up to 2 years | — |
| donor versus leukemia effect | 2 years | Analysis of donor WT1 positive CD8 T cells by flow cytometry |
Countries
China
Contacts
Primary ContactAI HUISHENG, MD
Outcome results
None listed