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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: microtransplantation; Biological: HLA-mismatched donor peripheral stem cell infusion

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 Type: Interventional
• Enrollment (Anticipated): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Affiliated Hospital of Academy of Military Medical Sciences ,
      • Contact: AI HUISHENG, MD; Phone Number: 86-1066947126; Email: HUISEHNGAI@163.COM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-related mortality	Early mortality: death within 4 weeks after initiation of induction therapy	2 years
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	Analysis of donor WT1 positive CD8 T cells by flow cytometry	2 years
recipient versus leukemia effect	Analysis of recipient WT1 positive CD8 T cells by flow cytometry	2 YEAR

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
• Investigators: Principal Investigator: AI HUISEHNG, MD, Affiliated Hospital of Academy of Military Medical Sciences

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: June 17, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; stem cell; donor; infusion; Peripheral; elderly patients; microtransplantation; HLA-mismatched
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IMCG-EAML2014