IMCG-EAML: Safety and Efficacy Study of Microtransplantation to Treat Elderly Acute Myeloid Leukemia

Sponsor

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

Overall Status

Unknown status

CT.gov ID

NCT02171117

Collaborator

(none)

196

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Procedure: microtransplantation Biological: HLA-mismatched donor peripheral stem cell infusion	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

196 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2014

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Jun 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

No Intervention: CT-group

standard induction and consolidation chemotherapy only, without microtransplantation

Experimental: MST-group

standard induction and consolidation chemotherapy with microtransplantation

Procedure: microtransplantation

infusion of granulocyte colony stimulating factor (G-CSF) mobilized HLA-mismatched peripheral blood stem cells (GPBSC)

Other Names:

DSI

Biological: HLA-mismatched donor peripheral stem cell infusion

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

treatment-related mortality [2 years]
Early mortality: death within 4 weeks after initiation of induction therapy
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
recipient versus leukemia effect [2 YEAR]
Analysis of recipient WT1 positive CD8 T cells by flow cytometry

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.