A Prospective, Multicenter, and Exploratory Study of CMGV in the Treatment of Recurrent Adult AML and MDS-EB-2/Elder AML

A Prospective, Multicenter, and Exploratory Study of Mitoxantrone Liposomes, Cytarabine and G-CSF Combined With Vineclavone in the Treatment ofRecurrent Adult AML and MDS-EB-2/Elder AML

The goal of this clinical trial] is to evaluate mitoxantrone hydrochloride liposomes, subcutaneous injection of cytarabine and G-CSF combined with Venetoclax (CMG+Ven) in adult secondary acute myeloid leukemia and myelodysplastic syndrome with increased primordial cells type 2(MDS-IB2) or elderly acute myeloid leukemia]. The main questions it aims to answer are:

• Evaluation of the efficacy
• Evaluation of the safety

Study Overview

• Status: Recruiting
• Conditions: Recurrent Adult Acute Myeloid Leukemia; Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CMGV

Detailed Description

Mitoxantrone is a traditional anthracycline drug. It exerts anti-tumor effects by interfering with DNA, RNA and inhibiting topoisomerase II. It is a cell cycle non-specific drug ; Mitoxantrone has been used in AML patients. It is widely used in both induction and relapse and refractory treatment stages . At the same time, the literature shows that there is no complete cross-resistance between mitoxantrone and other anthracycline drugs, and it is still effective for patients who have relapsed after previous first-line anthracycline treatment . In addition, the CMG (standard dose cytarabine + mitoxantrone + G-CSF) prestimulation regimen has many applications in China ; a study showed that 16 cases of elderly AML (50% were early in the elderly The CR rate of the CMG regimen for the treatment of secondary AML was 50%, the ORR was 87.4%, and the median OS was 12 months in 2006; a study applied the CMG regimen vs. the conventional dose MA regimen (mitoxantrone + arabinoside Glucoside) in the treatment of elderly AML, the results showed that there was no significant difference in efficacy between the two regimens, but the CMG group had a shorter bone marrow suppression period and less bleeding and infection than the MA group in 2014. Since there is no drug for mitoxantrone in the domestic market for a long period of time, its clinical application is limited. Mitoxantrone Hydrochloride Liposomal Injection is a Class 2 new drug independently developed by CSPC. It will be launched in China in 2022. The approved indications are: those who have received at least first-line standard treatment (including chemotherapy, autologous hematopoietic stem cell transplantation, etc.) For patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), the registration key phase II clinical trial showed good therapeutic effects in relapsed or refractory PTCL and NKTCL, with a confirmed ORR of 41.7%; among them, NKTCL subtype The type has remarkable efficacy, breaking through the limitations of NKTCL's natural resistance to anthracyclines in previous clinical experience. The ORR of single-drug treatment can reach 42.9%.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: xiaoqian Xu, Doctor; Phone Number: 13816205940; Email: Ellenxxq@qq.com
• Study Contact Backup: Name: Sujiang Zhang, Doctor; Email: zbruce.zhang@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Ruijin Hospital
      • Contact: xiaoqian Xu, Doctor; Phone Number: 13816205940; Email: Ellenxxq@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient fully understands this study, voluntarily participates and signs an informed consent form (ICF);
• Age: 18-75 years old (including boundary values of 18 and 75);

• Clinically confirmed adult AML and MDS-IB2 (WHO 2022 standard) patients, AML patients meet any of the following criteria:

  1. Treatment related AML
  2. Previously had a history of MDS
  3. Associated with MDS related genes/chromosomal abnormalities
  4. Previously had a history of CMML
  5. Age ≥ 60 years old
  6. Previous history of prodromal MPN, including ET, PV, and MF, with bone marrow fibrosis ≤ grade 2 (according to the 0-3 grade standard)；
• For elderly AML or MDS patients, the comprehensive evaluation should be based on the Fit population: ECOG<3, no major comorbidities, and MMSE and SPPB meet the standards (refer to Appendix 8-11);
• Expected survival time ≥ 3 months;
• Liver and kidney function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal value (ULN) (≤ 5 times the upper limit of normal value for patients with liver infiltration); Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver infiltration); Serum creatinine ≤ 1.5 times the upper limit of normal value;
• The relevant treatment for MDS (excluding blood transfusion) must be completed 2 weeks before the start of the study treatment; In the case of rapidly proliferative diseases, hydroxyurea is allowed to be used until 24 hours before the start of the study treatment. Before starting the research treatment,Toxicity related to previous MDS treatment must be restored to level 2 or below.

Exclusion Criteria:

The researchers determined that patients who are not suitable to participate in this study. If a patient meets any of the following criteria, they will not be allowed to enter this study:

• The subject's previous history of anti-tumor treatment meets one of the following conditions:

  1. Individuals who have previously received mitoxantrone or mitoxantrone liposomes;
  2. Previously received treatment with doxorubicin or other anthracyclines, with a total cumulative dose of doxorubicin>360mg/m2 (1mg of doxorubicin is equivalent to 2mg of doxorubicin or 0.5mg of doxorubicin);
  3. Within 4 weeks prior to the first use of the study drug or within 5 half-lives of the drug, the patient has received anti-tumor treatment including surgery, chemotherapy, targeted therapy, or participated in other clinical trials and received clinical trial medication;

• Heart function and disease meet one of the following conditions:

  1. Long QTc syndrome or QTc interval>480ms;
  2. Complete left bundle branch block, II or III degree atrioventricular block;
  3. Severe and uncontrolled arrhythmias that require medication treatment;
  4. The New York College of Cardiology in the United States has a classification of ≥ II;
  5. Cardiac ejection fraction (LVEF) below 50%;
  6. A history of myocardial infarction, unstable angina, severe unstable ventricular arrhythmias, or any other arrhythmias requiring treatment, a history of clinically severe pericardial disease, or evidence of acute ischemic or active conduction system abnormalities on electrocardiogram within the 6 months prior to recruitment.
• Patients who have previously or currently suffered from other malignant tumors (except for effectively controlled non melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have not been treated for more than 6 months and have been effectively controlled, as well as patients who have received long-term non chemotherapy treatments such as hormone therapy);
• Uncontrollable systemic diseases (such as infection during the promotion period, uncontrollable hypertension, diabetes, etc.);
• Central nervous system leukemia;
• Secondary AML patients with bone marrow fibrosis ≥ grade 3;
• CML patients with sudden changes;
• Accompanied by a well prognosis chromosome karyotype t (8; 21) (q22; q22.1) RUNX1:: RUNX1T1, inv (16) (p13.1 q22) CBFB: MYH11, as well as acute promyelocytic leukemia;
• Human immunodeficiency virus (HIV) infected individuals (HIV antibody positive);
• Active infection of hepatitis B and hepatitis C (if hepatitis B B surface antigen or core antibody is positive, HBV-DNA will be tested additionally, and if HBV-DNA exceeds 1x103 copies/mL, it will be excluded; if hepatitis C antibody is positive, HCV-RNA will be tested additionally, and if hepatitis C virus RNA exceeds 1x103 copies/mL, it will be excluded);
• Have a known history of immediate or delayed hypersensitivity reactions to similar drugs and excipients in the study drug;
• Accompanied by a history of severe neurological or mental illness;
• The researchers determined that there were patients who were not suitable to participate in this study.

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: CMGV regime; Mitoxantrone liposomes，Cytarabine，G-CSF，Venetoclax

Drug: CMGV; Initial treatment induction therapy: CMG+Vineclavone regimen Mitoxantrone liposomes 15mg/m2, iv, d1; Cytarabine 10mg/m2, H, q12h, d1-7; G-CSF starts at 5ug/kg, H, d0, WBC ≥ 30 × 109/L, stop G-CSF; Vinecla 100mg, 2200mg, 3400mg, d4-10. Every 4 weeks is a cycle, for a total of 2 cycles. For patients with CR/CRI/MLFS/PR in the first cycle, repeat this regimen for consolidation treatment once (the second course of treatment is Vineclavone 400mg d1-7). Follow up treatment: Patients who meet the transplantation criteria will undergo hematopoietic stem cell transplantation, while those who do not undergo transplantation will continue to receive CMG+Vineclavone consolidation for 4-6 courses.; Other Names: CMGV REGIME

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRc	CR (complete remission)+CRi (CR with incomplete recovery of hematological counts)	1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	1 year
OS	Overall Survival	2 year
RFS	Relapse-free survival	2 year
MRD-	Assessable residual lesion (MRD) conversion rate to negative	1 year
Adverse Event	Hematological and non hematological toxicit	1 year

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Sun Yat-sen University; Shanghai Zhongshan Hospital; RenJi Hospital; Huashan Hospital; Shanghai Public Health Clinical Center; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; First Hospital of China Medical University; Taizhou First People's Hospital; The Second Affiliated Hospital of Dalian Medical University; Shanghai Pudong Hospital; Xuhui Central Hospital, Shanghai; The Affiliated People's Hospital of Ningbo University; Huadong Hospital; Wenzhou People's Hospital; Dalian Municipal Central Hospital; Shanghai Jiading District Central Hospital; Army Medical Center of PLA
• Investigators: Principal Investigator: sujiang Zhang, Doctor, Hematological Depaement, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cytarabine; Venetoclax; Mitoxantrone Hydrochloride Liposomes; Recurrent Adult Acute Myeloid Leukemia; MDS-EB-2; Adult Acute Myeloid Leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence
• Other Study ID Numbers: CMG-sAML-001

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
• product manufactured in and exported from the U.S.: No