Sonrotoclax plus azacitidine with targeted agents or chemotherapy for newly diagnosed adult AML

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

This trial tests whether adding sonrotoclax to azacitidine, along with targeted drugs or chemotherapy, helps adults newly diagnosed with acute myeloid leukemia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 205 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (other)
• Drugs / interventions: gilteritinib, chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07548710 on ClinicalTrials.gov

What this trial studies

This open-label, phase II, multi-center trial combines sonrotoclax with azacitidine and individualized targeted agents or anthracycline chemotherapy in adults with newly diagnosed AML. Participants are stratified by FLT3/IDH1 mutation status and fitness for intensive chemotherapy, with fit patients receiving additional daunorubicin or idarubicin and FLT3-mutant patients receiving gilteritinib. Sonrotoclax is given with dose escalation from 20 mg/day up to 320 mg/day followed by maintenance dosing and possible temporary holds, while azacitidine is administered 75 mg/m² on Days 1–7 of each 28-day cycle. Safety and efficacy outcomes, including response rates and tolerability, are collected across treatment arms.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed non-APL AML, ECOG 0–3, WBC <25 × 10⁹/L (or reduced before treatment), and adequate liver and kidney function are the intended participants, with stratification by mutation status and fitness for intensive chemotherapy.

Not a fit: Patients with acute promyelocytic leukemia (APL), severe organ dysfunction beyond protocol limits, or those unable to attend the Shanghai study site are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, the combination could increase remission rates or extend remission duration for newly diagnosed AML patients, especially those treated with non‑intensive regimens.

How similar studies have performed: Similar combinations of BCL-2 inhibitors (notably venetoclax) with azacitidine have shown improved responses in older or unfit AML patients, supporting this combination approach though sonrotoclax itself is less established.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Yang Shen

Conditions: Acute Myeloid Leukemia, Newly Diagnosed Adult Acute Myeloid Leukemia, Sonrotoclax, Azacitidine