Mitoxantrone Hydrochloride Liposome, Standard-dose of Cytarabine and Venetoclax in the Treatment of R/R AML

NCT06621212 | Recruiting Phase 2

• 1 other identifier: CSPC-DED-AML-K16
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this prospective, multi-center, single-arm, phase 2 study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, standard-dose of cytarabine and venetoclax (MAV) in the treatment of relapsed or refractory (R/R) AML. The study plan to enroll 72 R/R AML patients who are expected to receive laboratory tests of bone marrow and blood specimens at regular times after MAV treatment.

Conditions

Relapsed/Refractory Acute Myeloid Leukaemia; Myeloid Malignancy

Outcome Measures

Primary Outcomes (1)

• Composite complete remission (CRc) rate

  Complete remission plus complete remission with incomplete hematologic recovery (CR+CRi). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.

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

Secondary Outcomes (6)

• Overall response rate (ORR)

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

• Relapsed free survival (RFS)

  up to 12 months

• Event free survival (EFS)

  up to 12 months

• overall survival (OS)

  up to 12 months

• Rate of CR/CRi without minimal residual disease

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

Study Arms (1)

MAV regimen

EXPERIMENTAL

First induction: Mitoxantrone hydrochloride liposome injection, cytarabine combined with venetoclax. Second induction: Patients who achieved PR or MLFS after the first induction cycle will receive re-induction therapy with the same initial regimen. Consolidation: For patients with CR/CRi, allo-HSCT is recommended. For those currently ineligible for allo-HSCT, age- and fitness-adapted consolidation is advised. For intensive chemotherapy: Cytarabine (\<60y: 2g/m² q12h d1-3; ≥60y: 1g/m² q12h d1-3) + Venetoclax 300mg d1-7, for 2-3 cycles. For non-intensive candidates, an appropriate regimen should be selected per investigator.

Drug: mitoxantrone hydrochloride liposome; Drug: Cytarabine; Drug: Venetoclax

Interventions

mitoxantrone hydrochloride liposome DRUG

Mitoxantrone hydrochloride liposome (30 mg/m\^2) on day 1, every 4 weeks

MAV regimen

Cytarabine DRUG

Cytarabine (100 mg/m\^2 ) on day 1-7, every 4 weeks

MAV regimen

Venetoclax DRUG

Venetoclax 100 mg on day 2，200 mg on day 3，400 mg on day 4-8, every 4 weeks

MAV regimen

Eligibility Criteria

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

You may qualify if:

• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
• Age ≥18
• Clinically diagnosed relapsed/refractory AML, excluding acute promyelocytic leukemia.
• Patients who failed after at least 1 courses of initial induction therapy.
• Bone marrow blasts≥5% after CR/CRi, or reappearance of blasts in the blood in at least 2 peripheral blood samples at least one week apart, or leukemia cell infiltration appeared in extramedullary.
• Conversion from MRD negativity to MRD positivity after CR/CRi.
• Physical status score of Eastern Oncology Collaboration Group (ECOG) 0-2.
• Life expectancy \> 3 months.
• AST/ALT≤2.5 ULN (for subjects with hepatic infiltration≤5 ULN); Total bilirubin≤1.5 ULN (for subjects with hepatic infiltration≤3 ULN); Serum creatinine≤1.5 ULN.

You may not qualify if:

• Previous anti-tumor therapy meets one of the following criteria:
• Prior therapy with mitoxantrone or mitoxantrone liposome;
• Prior therapy with doxorubicin or anthracyclines, and the cumulative dose of doxorubicin \> 360 mg/m\^2 (1 mg doxorubicin was equivalent to 2 mg daunorubicin or 0.5 mg idarubicin);
• Have received other anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, Chinese medicines with anti-tumor activity, except those that do not affect the efficacy of the study as determined by the investigator) or participated in other clinical trials and received clinical trial drugs within 4 weeks or 5 half-lives of the drug before the study;
• Subjects who received strong or moderate CYP3A inducers/inhibitors or P-glycoprotein (P-gp) inhibitors within 7 days before starting study treatment;
• Subjects who are unable to take oral medications or have malabsorption syndrome;
• Cardiovascular diseases, including but not limited to:
• QTc interval \>480 ms or long QTc syndrome in screening;
• Complete left bundle branch block, 2 or 3 grade atrioventricular block;
• Requiring treatment of serious and uncontrolled arrhythmia;
• New York Heart Association NYHA≥2;
• Cardiac ejection fraction (EF) was less than 50%;
• Myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other history of arrhythmia or clinically serious pericardial disease that requires treatment within the first 6 months of enrollment, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
• Central nervous system leukemia;
• Previous or current occurrence of other malignancies (in addition to non-melanoma basal cell carcinoma of the skin that is effectively controlled, breast/cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment within the past five years).

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Jie Jin, M.D.

CONTACT

+86 571-87236896; jiej0503@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: October 1, 2024
• Study Start: July 5, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

CN (1)