Dose-escalation Study of D-CMG Regimen for the Treatment of Elderly Newly Diagnosed AML Patients

Dose Escalation Study of Liposomal Mitoxantrone Hydrochloride Injection Combined With Decitabine and Cytarabine (D-CMG) for the Treatment of Elderly Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

to observe the dose-limiting toxicity (DLT) of liposomal mitoxantrone hydrochloride injection combined with cytarabine and decitabine in the initial treatment of acute myeloid leukemia (AML), to explore the maximum tolerated dose (MTD) of the combined D-CMG regimen, and to evaluate its safety and efficacy

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: D-CMG

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bing Xu; Phone Number: 18750918842; Email: xubingzhangjian@126.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Bing Xu, phD; Email: xubingzhangjian@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed acute myeloid leukemia (non-M3) that has not been previously treated and cannot receive standard cytarabine and anthracycline induction therapy due to age, comorbidities, or patient preference.
2. Aged 60-75 years, both male and female, with an expected survival time of more than 3 months.
3. Estimated creatinine clearance rate ≥ 30 mL/min.
4. AST and ALT ≤ 3.0 x ULN (unless considered due to leukemic organ involvement). Bilirubin ≤ 1.5 x ULN (unless considered due to leukemic organ involvement).
5. ECOG Performance Status ≤ 2.
6. Able to understand and voluntarily provide informed consent.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL) and low-risk cytogenetics, such as t(8;21), inv(16), or t(16;16).
2. Active central nervous system leukemia.
3. History of myeloproliferative neoplasms (MPN), including myelofibrosis, primary thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, and AML with BCR-ABL1 translocation.
4. HIV-positive patients and/or active HBV or HCV infection (as documented by positive HBV-DNA and HCV-RNA tests).
5. Clinically significant QTc prolongation (men > 450 ms; women > 470 ms), ventricular tachycardia, atrial fibrillation, second-degree heart block, history of myocardial infarction within the past year, congestive heart failure, and coronary artery disease requiring medication.
6. Active, uncontrolled severe infection.
7. History of other malignancies within the past 2 years, except for adequately treated in situ carcinoma of the cervix or breast; skin basal cell carcinoma or localized squamous cell carcinoma of the skin.
8. White blood cell count > 25 x 10^9/L. (This criterion can be met with hydroxyurea or leukapheresis.)
9. Mental impairment that would compromise the ability to participate in the study.
10. Any other situation in which the investigator believes that it would not be in the best interest of the patient to participate in the trial.

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: D-CMG; Liposomal mitoxantrone hydrochloride injection (Doxorubicin®): Used after dilution with 250mL of 5% glucose injection (50mg/mL), with an intravenous drip time of at least 60 minutes.; Level 1: 12mg/m2, IV drip, day 4;; Level 2: 18mg/m2, IV drip, day 4; Decitabine: 25mg, IV drip, days 1-3; Cytarabine: 10mg/m2, every 12 hours, IV drip, days 4-10; G-CSF: 300 ug, IV drip, days 1-5; Each cycle is 4 weeks, with a total of 2 cycles, and DLT is observed in the first cycle. Note: Patients who achieve CR (Complete Remission) and PR (Partial Remission) in the first cycle can continue with the original dose for one more cycle, and then the investigator decides whether to continue this regimen or choose another regimen for maintenance therapy; Patients with NR (No Remission) in the first cycle will be withdrawn from this study.

Drug: D-CMG; Liposomal mitoxantrone hydrochloride injection (Doxorubicin®): Used after dilution with 250mL of 5% glucose injection (50mg/mL), with an intravenous drip time of at least 60 minutes.; Level 1: 12mg/m2, IV drip, day 4;; Level 2: 18mg/m2, IV drip, day 4; Decitabine: 25mg, IV drip, days 1-3; Cytarabine: 10mg/m2, every 12 hours, IV drip, days 4-10; G-CSF: 300 ug, IV drip, days 1-5; Each cycle is 4 weeks, with a total of 2 cycles, and DLT is observed in the first cycle. Note: Patients who achieve CR (Complete Remission) and PR (Partial Remission) in the first cycle can continue with the original dose for one more cycle, and then the investigator decides whether to continue this regimen or choose another regimen for maintenance therapy; Patients with NR (No Remission) in the first cycle will be withdrawn from this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Defined as the highest dose at which less than 2 out of 6 (ie. 33%) participants experience a Dose-Limiting Toxicity (DLT).	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CR)	The percent of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML)	Up to 24 months
Complete Response with incomplete blood count recovery (CRi)	Meets all CR criteria, except for residual neutropenia < 1,000/µL or hrombocytopenia < 100,000/µL. Dependence on red blood cell (RBC) transfusions is also defined as CRi.	Up to 24 months
Disease free survival (DFS)	Applies only to patients who achieve CR or CRi. It is measured from the date of remission to the date of relapse or death from any cause.	Up to 24 months
Overall survival (OS)	Time from the start of the patient's initial treatment to the time of death due to any cause.	Up to 24 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Investigators: Principal Investigator: Bing Xu, The First Aiffiliated hosptical of xiamen University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 19, 2024
• First Submitted That Met QC Criteria: October 19, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: XMDYYYXYK-14

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