Microtransplantation Combined With Azacytidine to Improve the Efficacy of EAML

A Multicenter Clinical Study of Microtransplantation Combined With Azacytidine to Improve the Efficacy of Elderly Acute Myeloid Leukemia

Patients enrolled from each center according to confirmed criteria specified in cooperative scheme are recieved induction and consolidation chemotherapy with microtransplantation . Observe the remission rate and 2-year disease-free survival (DFS) and overall survival(OS) rate.

Study Overview

• Status: Recruiting
• Conditions: Adult Acute Myeloid Leukemia
• Intervention / Treatment: Biological: microtransplantation, HLA-mismatched donor peripheral stem cell infusion; Drug: Azacitidine; Drug: Venetoclax

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.

In this study, azacytidine, decitabine, BCL / 2 inhibitor and other drugs combined with micro transplantation were used in elderly AML in order to improve the curative effect.

Patients enrolled from each center according to confirmed criteria specified in cooperative scheme are recieved induction and consolidation chemotherapy with microtransplantation . Observe the remission rate and 2-year disease-free survival (DFS) and overall survival(OS) rate.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yajing huang; Phone Number: +8615811031508; Email: yajing_huang@163.com
• Study Contact Backup: Name: mei guo; Phone Number: +8615811031508; Email: 15811031508@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • The Fifth Medical Center of PLA General Hospital
      • Contact: yajing huang; Phone Number: +8615811031508; Email: yajing_huang@163.com
      • Contact: mei guo; Phone Number: +8615811031508; Email: 15811031508@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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MST for unfit; Induction chemotherapy can use azacytidine combined with low-dose cytarabine, or azacytidine combined with BCL / 2 inhibitor, and infuse modified peripheral blood hematopoietic stem cells after chemotherapy. Consolidation chemotherapy used azacytidine combined with low-dose cytarabine. After chemotherapy, modified peripheral blood hematopoietic stem cells were infused and repeated for 3 courses.

Biological: microtransplantation, HLA-mismatched donor peripheral stem cell infusion; HLA-mismatched donor peripheral stem cell infusion; Other Names: DSI; Drug: Azacitidine; azacytidine 50-75mg/m2; Other Names: Demethylated drugs; Drug: Venetoclax; Venetoclax 100-300mg/d ×3d，400mg 4-28d; Other Names: BCL/2 inhibitor

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;	2month

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 year
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 year

Collaborators and Investigators

• Sponsor: guomei

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: MST-EAML2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No