Aclarubicin Plus With Azacitidine and Venetoclax in the Treatment of Acute Myeloid Leukemia

NCT07486726 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: AVAIL 2025
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 4

Brief Summary

Acute myeloid leukemia Acute myeloid leukemia (AML) is a clonal hematopoietic cancer that disrupts normal hematopoiesis, ultimately leading to bone marrow failure and death. The annual incidence rate of AML is 4.1 per 100000 people in the US and is higher in patients older than 65 years. There has been a steady improvement in survival over the decades, more noticeably so in younger patients and in the last decade. Azacitidine and Venetoclax is now the standard treatment of newly diagnosed AML ineligible for intensive chemotherapy, while still facing the dilemma of relapse and refractory disease. Anthracycline-based chemotherapeutics were wildly used in the treatment of fit AML patients. While the cardiovascular toxicity leading to morbidity and mortality limited the use of daunorubicin/idarubicin in unfit patients. Aclarubicin, also known as aclacinomycin A, is an anthracycline type of antibiotic with significant anti-cancer properties. Previous studies have shown that aclarubicin only induces histone eviction without causing DNA damage, and it stands out in pre-clinical models and clinical studies, as it potently kills AML cells. Meanwhile, aclarubicin lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. CAG regimen, combined with low-dose cytarabine, aclarubicin and G-CSF has been widely used in China and Japan for treatment of AML. The purpose of this study is to determine the maximum tolerated dose, safety and efficacy of aclarubicin combined with azacitidine and venetoclax for subjects with newly diagnosed and relapsed /refractory AML.

Conditions

Acute Myeloid Leukemia (AML); Relapse Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia (AML)

Keywords

acute myeloid leukemia; Aclarubicin; ineligible for intensive chemotherapy; Azacitidine and Venetoclax

Outcome Measures

Primary Outcomes (4)

• 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)

Secondary Outcomes (3)

• Composite Complete Remission (CCR)

  Proportion of patients who achieved CR+CRi+CRh at the end of Cycle 2 (each cycle is 28 days)

• Complete Remission Rate (CRR)

  Proportion of patients who achieved CR at the end of Cycle 2 (each cycle is 28 days)

• Adverse Events

  From enrollment through 28 days after the end of the last dose of aclarubicine

Other Outcomes (3)

• Association between baseline genomic alterations and composite complete remission (CCR)

  From baseline to first documented composite complete remission, assessed up to 24 weeks

• Change in quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) global health status score

  From enrollment through 28 days after the end of the last dose of aclarubicine

• Cancer-related fatigue as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score

  From enrollment through 28 days after the end of the last dose of aclarubicine

Study Arms (1)

Aclarubicin + Venetoclax + Azacitidine

EXPERIMENTAL

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 determined by the dose escalation.

Drug: Aclarubicin; Drug: Venetoclax; Drug: Azacitidine

Interventions

Aclarubicin DRUG

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

Aclarubicin + Venetoclax + Azacitidine

Venetoclax DRUG

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

Aclarubicin + Venetoclax + Azacitidine

Azacitidine DRUG

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

Aclarubicin + Venetoclax + Azacitidine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• Leiden University Medical Center: collaborator
• Fred Hutchinson Cancer Center: collaborator
• Washington University School of Medicine: collaborator

Study Sites (4)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

Shanghai, China

Location

Shanghai Jing'an District Beizhan Hospital

Shanghai, China

Location

Shanghai Traditional Chinese Medicine Hospital

Shanghai, China

Location

Tongren Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Aclarubicin; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Junmin Li, Professor

  Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunxiang Zhang

CONTACT

+86-13564516004; zyx12103@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of hematology

Model Details: Phase I Primary Objectives: Evaluate safety and tolerability of aclarubicin + azacitidine + venetoclax in newly diagnosed AML patients unfit for intensive induction therapy. Phase II Primary Objectives: To determine the efficacy of the triplet regimen in two cohorts. Cohort A: newly diagnosed AML, who are unfit for, or who refuse, intensive induction therapy Cohort B: AML relapsed/refractory after intensive chemotherapy (Exclude patients with FLT3 or IDH1/2 mutations who have not previously received targeted therapy)

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: March 20, 2026
• Study Start: March 15, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)