Study of SA+X in the Treatment of Newly Diagnosed AML

Clinical Study of Sonrotoclax Combined With Azacitidine Plus Individualized Targeted Drugs in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia

This is a phase II, open-label, multi-center study evaluating the efficacy and safety of sonrotoclax (SA) in combination with azacitidine (AZA) plus individualized targeted or chemotherapeutic agents in adult participants with newly diagnosed acute myeloid leukemia (AML). Eligible participants will be stratified into different treatment arms based on genetic background (FLT3/IDH1 mutation status) and fitness for intensive chemotherapy. All participants will receive sonrotoclax with dose escalation from 20 mg/day to 320 mg/day, followed by maintenance dosing, which may be temporarily held by the investigator from Day 14 to Day 28 of each 28-day cycle based on the participant's condition, combined with azacitidine 75 mg/m²/day intravenously on Days 1-7. For participants fit for intensive chemotherapy, additional anthracycline (daunorubicin 60 mg/m²/day or idarubicin 10 mg/m²/day on Days 1-3) will be administered. For participants with FLT3 mutations, gilteritinib 80 mg once daily on Days 1-14 will be added; for those with IDH1 mutations, ivosidenib 500 mg once daily on Days 1-28 will be added.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Sonrotoclax; Drug: Azacitidine (AZA); Drug: Gilteritinib; Drug: Ivosidenib; Drug: Anthracycline

• Study Type: Interventional
• Enrollment (Estimated): 205
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Shen; Phone Number: +86-021-64370045; Email: sy_clinicaltrial@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
      • Contact: Yang Shen; Phone Number: +86-021-64370045; Email: cxj0524@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed AML confirmed by bone marrow morphology and immunophenotyping (5th edition WHO diagnostic criteria)
• Subjects with APL excluded according to fusion gene and chromosome results
• ECOG performance status 0-3
• Age ≥ 18 years
• White blood cell count must be < 25 × 10⁹/L at the start of study treatment (can be reduced by leukapheresis and/or hydroxyurea)
• Subjects must have adequate organ function, defined as follows: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), unless elevated due to leukemic organ involvement; serum total bilirubin < 3 × ULN; higher levels are acceptable if attributable to ineffective erythropoiesis, leukemic organ involvement, or Gilbert syndrome; serum creatinine < 3 × ULN, or estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula
• Written informed consent obtained from the subject or legal representative

Exclusion Criteria:

• FAB classification as M3, or molecularly confirmed APL
• Refractory / relapsed subjects
• Subjects with a history of myeloproliferative neoplasms (MPN);
• Subjects with a history of myelodysplastic syndromes (MDS);
• Subjects with a history of chronic myeloid leukemia (CML);
• Subjects with mixed phenotype acute leukemia (MPAL);
• Documented central nervous system leukemia; or documented extramedullary leukemia (e.g., myeloid sarcoma, skin infiltration), excluding liver, spleen, and lymph node involvement;
• Hypersensitivity or allergy to any of the study drugs;
• Physical conditions or organ system dysfunction that impairs the ability to swallow capsules or tablets, or significantly affects gastrointestinal function and/or absorption (including malabsorption syndrome, small bowel resection, or uncontrolled inflammatory bowel disease);
• Cardiac conditions meeting any of the following:a) Long QT syndrome or QTc interval > 480 ms;b) Second- or third-degree atrioventricular block; severe, uncontrolled arrhythmia requiring medical treatment;c) History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other treatable arrhythmia, clinically significant pericardial disease within 6 months prior to enrollment; or electrocardiographic evidence of acute ischemia or active conduction system abnormalities;
• Previous or current concurrent malignancy other than adequately controlled non-melanoma skin basal cell carcinoma, in situ breast/cervical carcinoma, or other malignancies adequately controlled without treatment for more than 6 months;
• Significantly abnormal liver or renal function (serum bilirubin, AST, ALT, or serum creatinine > 3 × upper limit of normal; excluding those deemed by the investigator to be related to AML);
• Subjects who have received previous anti-AML therapies other than hydroxyurea for cytoreduction, including but not limited to BCL-2, FLT3, IDH1 inhibitors, or other investigational agents;
• Coagulopathy unrelated to AML;
• HIV infection, syphilis infection, HCV infection, or active HBV infection (HBsAg positive; or HBsAg negative / HBcAb positive with HBV DNA > 1.0 × ULN);
• Other uncontrolled active infection (as judged by the investigator);
• Pregnant or breastfeeding women;
• Unable to understand or comply with the study protocol;
• Participation in other relevant clinical studies within 30 days (excluding diagnostic studies);
• Subjects deemed inappropriate for study participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SA+Anthracycline	Drug: Sonrotoclax; For all the participants who are eligible for this trial, Sonrotoclax (SON): 20 mg/day on Day 1, 40 mg/day on Day 2, 80 mg/day on Day 3, 160 mg/day on Day 4, and 320 mg/day on Days 5-28 of a 28-day cycle; the administration of SON may be temporarily held by the investigator from Day 14 to Day 28 based on the participant's condition.; Drug: Azacitidine (AZA); For all the participants who are eligible for this trial, Azacitidine (AZA): 75 mg/m² per day on Days 1-7.; Drug: Anthracycline; For FLT3/IDH1 wild-type participants who are eligible for chemotherapy, Anthracycline: Daunorubicin (DNR) 45 mg/m² per day on Days 1-3, or Idarubicin (IDA) 6 mg/m² per day on Days 1-3.
Experimental: SA+FLT3 inhibitor	Drug: Sonrotoclax; For all the participants who are eligible for this trial, Sonrotoclax (SON): 20 mg/day on Day 1, 40 mg/day on Day 2, 80 mg/day on Day 3, 160 mg/day on Day 4, and 320 mg/day on Days 5-28 of a 28-day cycle; the administration of SON may be temporarily held by the investigator from Day 14 to Day 28 based on the participant's condition.; Drug: Azacitidine (AZA); For all the participants who are eligible for this trial, Azacitidine (AZA): 75 mg/m² per day on Days 1-7.; Drug: Gilteritinib; For FLT3 mutant participants, FLT3 inhibitor (FLT3i): Gilteritinib 80 mg once daily on Days 1-14.
Experimental: SA+IDH1 inhibitor	Drug: Sonrotoclax; For all the participants who are eligible for this trial, Sonrotoclax (SON): 20 mg/day on Day 1, 40 mg/day on Day 2, 80 mg/day on Day 3, 160 mg/day on Day 4, and 320 mg/day on Days 5-28 of a 28-day cycle; the administration of SON may be temporarily held by the investigator from Day 14 to Day 28 based on the participant's condition.; Drug: Azacitidine (AZA); For all the participants who are eligible for this trial, Azacitidine (AZA): 75 mg/m² per day on Days 1-7.; Drug: Ivosidenib; For IDH1 mutant participants, IDH1 inhibitor (IDH1i): Ivosidenib 500 mg once daily on Days 1-28.
Experimental: SA	Drug: Sonrotoclax; For all the participants who are eligible for this trial, Sonrotoclax (SON): 20 mg/day on Day 1, 40 mg/day on Day 2, 80 mg/day on Day 3, 160 mg/day on Day 4, and 320 mg/day on Days 5-28 of a 28-day cycle; the administration of SON may be temporarily held by the investigator from Day 14 to Day 28 based on the participant's condition.; Drug: Azacitidine (AZA); For all the participants who are eligible for this trial, Azacitidine (AZA): 75 mg/m² per day on Days 1-7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite Complete Remission	At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal Residual Disease (MRD) Negativity Rate		At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).
Overall Response Rate		At the end of 2 cycles of induction therapy with the SA+X regimen (each cycle is 28 days); at the end of 4 cycles of induction therapy with the SA regimen (each cycle is 28 days).
Overall Survival		Time from enrollment to all-cause death within 3 years
Event-free Survival		Time from enrollment to treatment failure, relapse, or death from any cause within 3 years
Adverse Events	According to the CTCAE Version 6.0 criteria	From the start of induction to 30 days after the completion of treatment
Time to neutrophil and platelet recovery		From the start of induction to 30 days after the completion of treatment

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 21, 2028

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Azacitidine; Sonrotoclax; Newly Diagnosed Adult Acute Myeloid Leukemia
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Naphthacenes; Aminoglycosides; Azacitidine; gilteritinib; ivosidenib; Anthracyclines
• Other Study ID Numbers: SAXUM_2026

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes