Trial Radar AI | ||
|---|---|---|
Clinical Trial NCT07486726 for Acute Myeloid Leukemia (AML), Relapse Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia (AML) is not yet recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Shanghai Jiao Tong University School of MedicineAclarubicin Plus With Azacitidine and Venetoclax in the Treatment of Acute Myeloid Leukemia Phase 1, Phase 2 112
Phase I is open to patients with newly diagnosed AML who's not a candidate for, or refusal of intensive induction therapy. This will be followed by two parallel phase II e...
Show MoreA Multicenter, Open-Label, Phase 1/2 Clinical Study of the Safety and Efficacy of Aclarubicin Combined With Azacitidine and Venetoclax in the Treatment of Acute Myeloid Leukemia
- AVAIL 2025
Phase 2
Aclarubicin
ineligible for intensive chemotherapy
Azacitidine and Venetoclax
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ExperimentalAclarubicin + Venetoclax + Azacitidine Aclarubicin will be used in a dose escalation and dose expansion approach. Venetoclax and aclarubicin will be used in a fixed dose throughout the phases.
Phase I dose-escalation: a standard "3+3" approach for aclarubicin. Phase II: Cohort A will enroll patients same as in phase I and Cohort B will enroll patients with relapsed/refractory AML after intensive chemotherapy. Aclarubicin will be used at the dose determin...Show More | Aclarubicin Induction (Cycle1) Phase I starting dose 20mg/m\^2 D1-D2 (dose group 1), 20mg/m2 D1-D3 (dose group 2), 20mg/m2 D1-D4 (dose group 3), ivgtt, Qd The Phase II dose was determined based on the Phase I results
Consolidation (Cycle 2-6) Phase I starting dose 20mg/m\^2 D1-D2 (dose group 1), 20mg/m2 D1-D3 (dose group 2), 20mg/m2 D1-D4 (dose group 3), ivgtt, Qd The Phase II dose was determined based on the Phase I results Venetoclax Cycle 1 (Induction) 100mg on day 1, 200mg on day 2, 400mg on days 3-14
Cycles 2-6 (Consolidation) 400 mg orally daily on days 1-7 Azacitidine Cycle 1 (Induction) 75 mg/m\^2 SC on days 1-7 of each cycle
Cycles 2-6 (Consolidation) 75 mg/m\^2 SC on days 1-7 of each cycle
Cycles 7-18 (Maintenance) 50 mg/m\^2 SC on days 1-5 of each cycle |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Maximum tolerated dose (MTD) | MTD for aclarubicin (primary outcome measure of phase I) | 28 days after first dose of aclarubicin |
Recommended Phase 2 Dose (RP2D) | RP2D for aclarubicin (primary outcome measure of phase I) | 28 days after first dose of aclarubicin |
Event-free survival (EFS) | primary outcome measure of phase II, cohort A | From date of enrollment until the date of induction treatment failure , relapse for patients who achieved induction treatment success, or death from any cause, whichever came first, assessed up to 24 months |
Composite Complete Remission (CCR) | primary outcome measure of phase II, cohort B | Proportion of patients who achieved CR+CRi+CRh at the end of Cycle 2 (each cycle is 28 days) |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Composite Complete Remission (CCR) | Preliminary efficacy assessment (secondary outcome measure of phase I). Proportion of patients who achieved CR+CRi+CRh. | Proportion of patients who achieved CR+CRi+CRh at the end of Cycle 2 (each cycle is 28 days) |
Complete Remission Rate (CRR) | Preliminary efficacy assessment (secondary outcome measure of phase I). Proportion of patients who achieved CR. | Proportion of patients who achieved CR at the end of Cycle 2 (each cycle is 28 days) |
Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v6.0 | From enrollment through 28 days after the end of the last dose of aclarubicine |
Understand and voluntarily sign the informed consent form.
Age 18 or above.
Diagnosis (the diagnose is based on the 5th edition of the WHO classification of hematolymphoid tumors):
- Phase I cohort: Adults ≥18 years with newly diagnosed AML who's not a candidate for intensive chemotherapy (criteria include age ≥75, significant cardiac/pulmonary/hepatic/renal comorbidities, CGA assessment unfit for IC, etc.) or declines.
- Phase II cohort A: Adults ≥18 years with newly diagnosed AML who's not a candidate for intensive chemotherapy (criteria include age ≥75, significant cardiac/pulmonary/hepatic/renal comorbidities, CGA assessment unfit for IC, etc.) or declines.
- Phase II cohort B: Adults ≥18 years with relapsed/refractory AML after intensive chemotherapy (Exclude patients with FLT3 or IDH1/2 mutations who have not previously received targeted therapy).
Performance status < 3 (ECOG Scale).
Estimated survival ≥ 3 months.
White blood cell (WBC) count < 25 × 10^9 cells/L (hydroxyurea is permitted to control WBC count before treatment).
Adequate liver and renal function as defined by the following criteria:
- Total serum bilirubin < 2.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN, unless due to the underlying leukemia approved by the PI
- Creatinine clearance ≥50 mL/min
Ability to swallow
Phase II Cohort B: Subjects have recovered from prior treatment toxicity to less than Grade 2 (per CTCAE v6.0), excluding the influence of the underlying disease. The following are excluded: alopecia, fatigue, hyperpigmentation, hypothyroidism stabilized with hormone replacement therapy, and peripheral neuropathy following chemotherapy.
Phase II Cohort B: Washout period from first dose of prior anti-cancer therapy
- at least 2 weeks after completion of cytotoxic chemotherapy
- at least 5 half-lives for non-cytotoxic drugs (if the 5 half-lives exceed 4 weeks, the washout period will still be calculated as 4 weeks). If the half-life is unclear, a washout period of >4 weeks will be considered
- at least 2 weeks after the first dose of anti-cancer traditional Chinese medicine.
Subjects of reproductive potential must use effective contraceptive measures from the time they sign the informed consent form until 6 months after the last dose of the trial medication. Furthermore, male subjects of reproductive potential must refrain from sperm donation from the time they sign the informed consent form until 6 months after the last dose of the trial medication.
Prior therapies
Phase I cohort: Patients with prior therapy are not eligible. Patients with a history of myeloproliferative disorders (MPNs), including primary myelofibrosis (PMF), polycythemia vera (PV), chronic myeloid leukemia (CML) excluding essential thrombocythemia (ET); or myelodysplasia-myeloproliferative neoplasms (MDS-MPNs), including chronic monocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML), and acute promyelocytic leukemia (APL) are not eligible.
Prior hydroxyurea or cytarabine given for purposes of cytoreduction is also allowed. Prior all trans-retinoic acid given for presumed acute promyelocytic leukemia is also allowed.
Phase II cohort A: Same as for Phase I cohort.
Phase II cohort B: Patients relapsed/refractory to prior lower intensity therapy for AML are not eligible. No restriction on number of prior therapies.
Patients suitable for and willing to receive intensive induction chemotherapy (for Phase I and Phase II cohort A).
Congenital long QT syndrome or QTcF >450 msec (male), >470 msec (female). Repeat EKGs after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria. In cases where QTcF >450/470 msec is considered to be falsely increased due to inaccurate automated reading and not clinically significant (e.g. due to bundle branch block), patients are still eligible if cardiologist reviews and documents that QTcF is ≤ 450 msec when manually measured.
Active serious infection not controlled by systemic antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria.
Active central nervous system leukemia, extramedullary AML (except liver/spleen/lymph nodes)
Known human immunodeficiency virus (HIV) seropositive. Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection.
Patients who have received an allo-HCT within 60 days of first receiving study medication must discontinue all immunosuppressants during study treatment.
Patients who have previously received CAR-T therapy.
Subjects with malabsorption syndrome or other comorbidities that prevent them from swallowing capsules or taking medications via the enteral route.
Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI.
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry. Prior recent treatment with corticosteroids, hydroxyurea and/or cytarabine (given for cytoreduction) is permitted.
Pregnant /lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception throughout the study period and for at least 6 months after the last dose of study drugs. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 6 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control throughout the study period and for at least 6 months after the last dose of study drugs.
Shanghai Jiao Tong University School of Medicine327 active studies to explore