VMAC+DLI Treatment of Patients With Relapse of AML After Allo-HSCT (VMAC+DLI)

Study on the Efficacy and Safety of VMAC Combined With Donor Lymphocyte Infusion (DLI) in the Treatment of Patients With Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

This clinical trial included 30 cases and aimed to understand the effectiveness and safety of the VMAC regimen combined with donor lymphocyte infusion (DLI) in the treatment of patients with acute myeloid leukemia who have relapsed after allogeneic hematopoietic stem cell transplantation.

The main questions it aims to answer are:

The safety and efficacy of VMAC combined with DLI in the treatment of allo HSCT recurrence in AML patients;

Study Overview

• Status: Recruiting
• Conditions: Relapse Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Mitoxantrone hydrochloride liposome

Detailed Description

venetoclax 400 mg/d (reduced to 100 mg when combined with an azole), d1-7; liposomal mitoxantrone 30 mg/m2/d, d1; cytarabine (Ara-C) 100 mg/m2/d, d1-7; cyclophosphamide (CY) 400 mg/m2/d, d2, 5)，and then rest for 1 day before giving cryopreserved donor stem cells.MNC1-2X10^8/kg infusion, low-dose (25 mg Bid), short-course treatment (2-3 weeks after DLI) oral cyclosporine (CSA) is added to prevent graft-versus-host disease starting 3 days before the infusion of cryopreserved stem cells.

Monitor the occurrence of serious infections, cardiac toxicity, GVHD and other adverse reactions during the medication process; Blood routine recovery or bone marrow re examination 4 weeks after DLI to evaluate the efficacy of one course of VMAC combined with DLI; The patient was followed up for 2 years to evaluate long-term efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xin Chen, Doctor; Phone Number: 13920985705; Email: chenxin@ihcams.ac.cn
• Study Contact Backup: Name: Xueou Liu, Doctor; Phone Number: 022-23909095; Email: ec@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital, China
      • Contact: Xin Chen, Doctor; Phone Number: 13920985705; Email: chenxin@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with AML confirmed by bone marrow morphology and morphological recurrence after allo-HSCT (proportion of bone marrow morphological blast cells ≥5%);
2. Age ≥18 years and ≤65 years old, regardless of gender;
3. Eastern Oncology The evaluation of physical status of the cooperative group (ECOG-PS) is 0-2 points;
4. An informed consent form must be signed before the start of the research procedure, and the patient himself or his immediate family members must sign the informed consent form. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the legal guardian or the patient's immediate family member will sign the informed consent form.

Exclusion Criteria:

Subjects who meet any of the following criteria shall not be enrolled in this study:

• 1) Secondary transplant patients;
• 2) Have a history of tumor and have received any treatment for this tumor in the past 3 years, except for superficial bladder cancer , basal cell or squamous cell carcinoma of the skin, cervical intraepithelial carcinoma (CIN) or prostate intraepithelial carcinoma (PIN);
• 3) Serological reactions of known HIV, active hepatitis B, and active hepatitis C virus positive or syphilis positive;
• 4) Suffering from mental illness or other conditions and unable to cooperate with the requirements of research treatment and monitoring;
• 5) Pregnant patients or patients who cannot take appropriate contraceptive measures during treatment;

• 6) Active heart disease, definition One or more of the following:

  1. Long QTc syndrome or QTc interval >480ms;
  2. Complete left bundle branch block, II or III degree atrioventricular block;
  3. Need for drug treatment or History of severe arrhythmia with clinical symptoms;
  4. New York Heart Association classification ≥ II;
  5. Left ventricular ejection fraction less than 50%;
  6. Myocardial infarction, unstable angina, severe myocardial infarction within 6 months before enrollment History of unstable ventricular arrhythmias or any other arrhythmias requiring treatment, clinically severe pericardial disease, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• 7) Transplantation from an unrelated donor;
• 8) Those deemed not suitable for enrollment by the researcher.

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: VMAC+DLI; VMAC regimen : Veneclatra (VEN) 400 mg/d (reduced to 100 mg when combined with an azole), d1-7; Mitoxantrone Liposomal 30 mg/m2, d1; Cytosine arabinoside(Ara-C) 100 mg/m2/d, d1-7; Cyclophosphamide (CTX) 400 mg/m2/d, d2, 5); After 1 day of rest, cryopreserved donor stem cells MNC1-2X10^8 /kg infusion, add low-dose (25 mg Bid) and short-course treatment (stop 2-3 weeks after DLI) oral cyclosporine (CSA) to prevent graft-versus-host disease (GVHD) 3 days before cryopreserved stem cell infusion.

Drug: Mitoxantrone hydrochloride liposome; Veneclatra (VEN) 400 mg/d (reduced to 100 mg when combined with an azole), d1-7; Mitoxantrone Liposomal 30 mg/m2, d1; Cytosine arabinoside(Ara-C) 100 mg/m2/d, d1-7; Cyclophosphamide (CTX) 400 mg/m2/d, d2, 5); After 1 day of rest, cryopreserved donor stem cells MNC1-2X10^8 /kg infusion, add low-dose (25 mg Bid) and short-course treatment (stop 2-3 weeks after DLI) oral cyclosporine (CSA) to prevent graft-versus-host disease (GVHD) 3 days before cryopreserved stem cell infusion.; Other Names: Cyclophosphamide; Venetoclax; Cytarabine,Cytosine arabinoside

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	All tumor target lesions disappear, no new lesions appear, and tumor markers are normal, maintained for at least 4 weeks	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PR	The maximum sum of diameters of tumor lesions decrease≥ 30% and is maintained for at least 4 weeks	1 year
ORR	CR+PR	1year
2-year OS	The time from the start of treatment to death due to any reason	2 years
DFS	The time from the start of treatment to disease recurrence or death from any cause	2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Xin Chen, Doctor, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Mitoxantrone liposome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Venetoclax; Cytarabine; Mitoxantrone
• Other Study ID Numbers: IIT2024002

Drug and device information, study documents

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