Mitoxantrone Hydrochloride Liposome, Cytarabine, G-CSF Plus Venetoclax vs. Azacitidine Plus Venetoclax for MDS-IB2 and Secondary/Elderly AML

NCT07735117 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: CSPC-DED-AML-K24
• Study Type: interventional
• Target: 168
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome, subcutaneous cytarabine and G-CSF combined with venetoclax (CMG+Ven) versus azacitidine combined with venetoclax (VA) in the treatment of adult myelodysplastic syndrome IB2 (MDS-IB2) and newly diagnosed secondary or elderly AML.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndromes (MDS)

Keywords

Acute myeloid leukemia; Myelodysplastic Syndromes; mitoxantrone hydrochloride liposome; Cytarabine; Granulocyte Colony-Stimulating Factor; Venetoclax; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Composite Complete Remission (CRc = CR + CRh + CRI) in Induction Therapy (Assessed via European LeukemiaNet [ELN] 2022 Criteria)

  Number of participants achieving composite complete remission (CRc), defined as complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete hematologic recovery (CRI), assessed at the end of each 28-day cycle (up to 2 cycles) using European LeukemiaNet \[ELN\] 2022 criteria.

  At the end of each cycle (each cycle is 28 days), up to 2 cycles

Secondary Outcomes (7)

• Proportion of Participants With Objective Response (ORR = CRC + Morphologic Leukemia-Free State [MLFS] + Partial Remission [PR]) in Induction Therapy (Assessed via European LeukemiaNet [ELN] 2022 Criteria)

  At the end of each cycle (each cycle is 28 days), up to 2 cycles

• Proportion of CRc-Achieving Participants With Measurable Residual Disease (MRD) Negativity (Assessed via Flow Cytometry Testing Per ELN 2022 Criteria)

  At the end of each cycle (each cycle is 28 days), up to 2 cycles

• Overall Survival (OS) Time (From Treatment Day 1 to Date of Death From Any Cause)

  Up to 1 years after the date of the last enrolled participants

• Relapsed-Free Survival (RFS) Time (From CRc Achievement to Hematologic Relapse or Death From Any Cause)

  Up to 1 years after the date of the last enrolled participants

• Event-Free Survival (EFS) Time (From Treatment Day 1 to Treatment Failure, Hematologic Relapse From CRc, or Death From Any Cause [Whichever Occurs First])

  Up to 1 years after the date of the last enrolled participants

Study Arms (2)

CMG+VEN

EXPERIMENTAL

Patients who achieve complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) following Cycle 1 will proceed to consolidation therapy. Patients achieving a partial response (PR) or a ≥50% reduction in bone marrow blasts after Cycle 1 will receive one additional cycle of re-induction therapy with the same CMG+Ven regimen (venetoclax 400 mg daily on Days 1-7). Those who subsequently attain CR, CRh, CRi, or MLFS after Cycle 2 will proceed to consolidation therapy. Patients with no response (NR) after Cycle 1, or with NR or PR after Cycle 2, will discontinue study treatment.

Drug: Mitoxantrone Hydrochloride Liposome; Drug: Cytarabine; Drug: Granulocyte Colony-Stimulating Factor(G-CSF); Drug: Venetoclax

VA

ACTIVE COMPARATOR

Patients who achieve complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) following Cycle 1 will proceed to consolidation therapy. Patients achieving a partial response (PR) or a ≥50% reduction in bone marrow blasts after Cycle 1 will receive one additional cycle of re-induction therapy with the same VA regimen. Those who subsequently attain CR, CRh, CRi, or MLFS after Cycle 2 will proceed to consolidation therapy. Patients with no response (NR) after Cycle 1, or with NR or PR after Cycle 2, will discontinue study treatment.

Drug: Venetoclax; Drug: azacitidine

Interventions

Mitoxantrone Hydrochloride Liposome DRUG

Mitoxantrone Hydrochloride Liposome: 15 mg/m², administered by intravenous drip (ivgtt) on day 1

CMG+VEN

Cytarabine DRUG

Cytarabine: 10 mg/m², administered subcutaneously (H) every 12 hours (q12h) on days 1-7

CMG+VEN

Granulocyte Colony-Stimulating Factor(G-CSF) DRUG

G-CSF: 5 μg/kg, administered subcutaneously (H) starting from day 0, and discontinued when WBC ≥ 20×10\^9/L

CMG+VEN

Venetoclax DRUG

Venetoclax: 100 mg on day 2, 200 mg on day 3, and 400 mg on days 4-10, administered orally (po)

CMG+VEN

azacitidine DRUG

Azacitidine: 75 mg/m\^2, administered subcutaneously (H) on days 1-7.

VA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. The patient fully understands the study, voluntarily participates, and signs the Informed Consent Form (ICF).
• \. Age: 18-75 years inclusive. 3. Patients with clinically confirmed adult AML or MDS-IB2 (according to WHO 2022 criteria or ICC 2022 criteria). AML patients must meet any of the following:
• Therapy-related AML
• Prior history of MDS
• Presence of MDS-related genetic/chromosomal abnormalities
• Prior history of CMML
• Age ≥ 60 years
• Prior history of antecedent MPN (including ET, PV, and MF) with bone marrow fibrosis ≤ grade 2 (on a 0-3 grade scale) 4. For elderly AML patients, comprehensive assessment must show they belong to the Fit population: ECOG \< 3, CCI ≤ 0, and MMSE and SPPB assessment results meeting the Fit population criteria.
• \. Liver and kidney function: ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver infiltration); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with liver infiltration); serum creatinine ≤ 1.5 × ULN.
• \. Expected survival ≥ 3 months. 7. Prior MDS-related therapy (excluding blood transfusions) must be completed at least 2 weeks before the start of study treatment. In cases of rapidly proliferative disease, hydroxyurea is permitted up to 24 hours before the start of study treatment. Toxicities from prior MDS therapy must have recovered to Grade 2 or lower before the start of study treatment.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from the study:
• Prior anti-cancer treatment history meeting any of the following:
• Prior treatment with mitoxantrone or mitoxantrone liposome.
• Prior treatment with venetoclax or hypomethylating agents.
• Prior treatment with doxorubicin or other anthracyclines, with a cumulative doxorubicin dose \> 360 mg/m\^2 (for other anthracyclines, 1 mg doxorubicin is equivalent to 2 mg daunorubicin or 0.5 mg idarubicin).
• Received anti-cancer treatment including surgery, chemotherapy, targeted therapy, etc., or participated in another clinical trial with investigational drug within 4 weeks or 5 half-lives before the first dose of study drug.
• Cardiac function or disease meeting any of the following:
• Long QTc syndrome or QTc interval \> 480 ms.
• Complete left bundle branch block, second-degree or third-degree atrioventricular block.
• Severe, uncontrolled arrhythmia requiring medication.
• New York Heart Association (NYHA) Class ≥ II.
• Left ventricular ejection fraction (LVEF) \< 50%.
• History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, clinically significant pericardial disease within 6 months before enrollment, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Concurrent uncontrolled malignancy other than adequately controlled non-melanoma skin basal cell carcinoma, carcinoma in situ of breast/cervix, or other malignancies that have been effectively controlled without treatment for \> 6 months and patients receiving long-term non-chemotherapy treatment (e.g., hormone therapy).
• Uncontrolled systemic disease (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus).

Sponsors & Collaborators

• Ruijin Hospital: lead
• CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cytarabine; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Organic Chemicals; Ribonucleosides

Study Officials

• Sujiang Zhang

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoqian Xu

CONTACT

13816205940; Ellenxxq@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: July 29, 2026
• Study Start: July 30, 2026
• Primary Completion (Estimated): July 20, 2028
• Study Completion (Estimated): July 31, 2029
• Last Updated: July 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share