AML
Conditions
Brief summary
This is a Phase I/II, single-arm, open-label clinical trial evaluating the safety and preliminary efficacy of a novel induction regimen combining Venetoclax, Azacitidine, and Liposomal Mitoxantrone (VAM) in adult patients with newly diagnosed Acute Myeloid Leukemia (AML) who are eligible for intensive chemotherapy. The study plans to enroll 30 participants. Patients will receive VAM induction therapy, followed by three cycles of intermediate-dose cytarabine consolidation and 12 cycles of Venetoclax plus Azacitidine maintenance. Allogeneic hematopoietic stem cell transplantation is recommended for high-risk or MRD-positive patients in remission.
Interventions
DRUGVenetoclax
BCL-2 inhibitor. Oral. Induction: 100 mg day 1, 200 mg day 2, then 400 mg days 3-9 or 3-14. Maintenance: 400 mg days 1-7.
DRUGAzacitidine
Hypomethylating agent. 75 mg/m²/day IV/SC on days 1-7 of induction and maintenance cycles.
Liposomal topoisomerase II inhibitor. 24 mg/m² IV on day 1 of each induction cycle.
DRUGCytarabine
Antimetabolite. Consolidation: 2 g/m² (age \<60) or 1 g/m² (age ≥60) q12h IV on days 1-3 for 3 cycles.
Recommended for high-risk or MRD+ patients after response.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with AML according to the WHO (2022) or ICC criteria, or with MDS/AML as defined by ICC (with 10%-20% blasts in the bone marrow) * Age ≥ 14 years, male or female. * Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-2. * Meet the following laboratory requirements (tests must be performed within 7 days prior to treatment): i. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the corresponding age group. ii. AST and ALT ≤ 2.5 times ULN for the corresponding age group. iii. Serum creatinine \< 1.5 times ULN for the corresponding age group. iv. Cardiac enzymes \< 2 times ULN for the corresponding age group. v. Left ventricular ejection fraction (LVEF) within the normal range as measured by echocardiography (ECHO).
Exclusion criteria
* Acute promyelocytic leukemia with PML::RARA fusion gene. * Acute myeloid leukemia with RUNX1::RUNX1T1 fusion gene. * Acute myeloid leukemia with BCR::ABL1 fusion gene. * Previously treated patients (defined as having received prior induction chemotherapy for AML/MDS; prior use of cytoreductive agents like hydroxyurea is allowed). * Concurrent active malignancy of other organs (requiring treatment). * Active cardiac disease, defined as one or more of the following: i. History of uncontrolled or symptomatic angina. ii. Myocardial infarction within 6 months prior to study enrollment. iii. History of clinically significant arrhythmia requiring medication or causing severe symptoms. iv. Uncontrolled or symptomatic congestive heart failure (\> New York Heart Association \[NYHA\] Class 2). * Active, uncontrolled infectious diseases (e.g., untreated tuberculosis, pulmonary aspergillosis). * Any other condition that, in the opinion of the investigator, makes the patient unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite complete remission rate after induction | up to 42 days |
Secondary
| Measure | Time frame |
|---|---|
| Event-free survival | Up to 2 years |
| Overall survival | Up to 5 years |
| Relapse-free survival | Up to 5 years |
| MRD negativity rate by flow cytometry and molecular methods (PCR/NGS) after 1 and 2 induction cycles | At the end of the first and second induction cycles |
| 30-day mortality | up to 30 days |
| 60-day mortality | up to 60 days |
Contacts
CONTACTHui Wei, MD
Outcome results
None listed