Phase II Study of Sonrotoclax Combined With Chemotherapy in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

NCT06497062 | Active Not Recruiting Phase 2

• 1 other identifier: BGB-11417-2001-IIT
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This single-armed study aims to investigate the safety and efficacy of sonrotoclax in combination with intensive chemotherapy in subjects with newly diagnosed AML. Subjects will be stratified based on the genetic risk classification of 2022 European LeukemiaNet (ELN) recommendations and MRD status to receive specific consolidation therapy after the induction therapy.

Conditions

Acute Myeloid Leukemia

Keywords

Sonrotoclax; Risk-stratified; Acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• EFS

  event free survival rate

  2-year

Secondary Outcomes (6)

• Composite complete remission rate

  Up to cycle 2 (each cycle is 28 days)

• The complete remission rate of MRD negative

  Up to cycle 2 (each cycle is 28 days)

• RFS

  Only for subjects who have achieved CR, CRh, or CRi; The time from the first attainment of eligible remission (CR, CRh, or CRi) after the start of treatment to the recording of disease recurrence or death, whichever occurs first. Up to 24 months

• OS

  up to 24 months

• AE, SAE

  up to 24 months

Other Outcomes (2)

• MRD and long-term survival

  up to 24 months

• HSCT rate

  up to 24 months

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

Experimental: Sonrotoclax combined with intensive chemotherapy. Subjects receive induction therapy consisting of sonrotoclax combined with a 3+7 regimen. According to the ELN risks and MRD status, subjects who achieve composite complete remission (CRc) proceed with consolidation therapy, and allogeneic hematopoietic stem-cell transplant (allo-HSCT) can be included per investigator's decision. After the consolidation, subjects will receive sonrotoclax combined with azacitidine (AZA) alternating with AZA monotherapy every 2 cycles as maintenance therapy until intolerable toxicity, 12 months, relapse, death, withdrawal of informed consent, or study termination determined by investigators, whichever occurs first.

Drug: sonrotoclax; Drug: idarubicin/daunorubicin; Drug: Cytarabine; Drug: Azacitidine; Procedure: allo-HSCT

Interventions

sonrotoclax DRUG

Orally once daily, on D5-14. A 4-day dose ramp-up is required for the first induction. The dosing regimen will be determined in the Safety Run-in phase. If a second induction is needed, dose ramp-up is not required. In the consolidation therapy phase, subjects in the group with favorable risk and MRD negative do not need to receive Sonrotoclax treatment, and subjects in the group with favorable risk and MRD positive, or with intermediate and adverse risk will receive sonrotoclax on D1-7 at the target dose determined in the safety run-in phase, dose ramp-up is not required. In the maintenance therapy phase, subjects will receive once daily sonrotoclax on D1-14 at the target dose determined in the safety run-in phase.

Also known as: BGB11417

Assigned Interventions

idarubicin/daunorubicin DRUG

idarubicin: On D1-3, intravenously, 10 mg/m\^2 for subjects aged \<60 years, 6 mg/m\^2 for subjects aged ≥60 years daunorubicin: On D1-3, intravenously, 60 mg/m\^2 for subjects aged \<60 years, 40 mg/m\^2 for subjects aged ≥60 years

Also known as: IDA/DNR

Assigned Interventions

Cytarabine DRUG

In induction therapy phase: intravenously, 100 mg/m\^2 on D1-7. In consolidation therapy phase: subjects with favorable-risk and MRD negative will receive cytarabine intravenously at 2 g/m\^2/q12h for those aged \<60 years, at 1g/m\^2/q12h for those ≥60 years on D1-3 or 3+7 regimen, and subjects with favorable-risk and MRD positive or intermediate or adverse-risk will receive cytarabine intravenously at 1 g/m\^2/d q12h on D1-3(in combination with sonrotoclax).

Also known as: Ara-c

Assigned Interventions

Azacitidine DRUG

75 mg/m\^2, subcutaneously, once daily, on D1-7

Also known as: AZA

Assigned Interventions

allo-HSCT PROCEDURE

Per standard of procedure

Assigned Interventions

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed untreated acute myeloid leukemia patients;
• Age range from 18 to 75 years old;
• The Eastern Cooperative oncology Group (ECOG) score is ≤ 2 points;
• The following organ functional conditions must be met:
• Liver function (bilirubin\<2mg/dL, AST and/or ALT\<3 x ULN)
• Renal function (blood creatinine clearance rate ≥ 30 mL/min)
• Cardiac function (left ventricular ejection fraction ≥ 50%)
• If the age is ≥ 60 years old, the following conditions must be further met;
• Charlson comorbidity index (CCI) ≤ 1
• Activity of Daily Living Scale (ADL)\>100
• No cognitive impairment, Mini Mental State Examination (MMSE) ≥ 28
• No impairment of living ability, Short Physical Performance Battery Protocol (SPPB) ≥ 9
• Women with fertility must have a negative serum pregnancy test ≤ 7 days before the first administration. In addition, they must use efficient contraceptive methods before the first dose of study medication, during the study treatment period, and for ≥ 180 days after the last dose of study medication.
• Non infertile males must use efficient contraceptive methods during the study treatment period and within ≥ 90 days after the last dose of the study medication. During this period, they are not allowed to donate sperm.
• The patient fully understands this study, obtains an informed consent form (ICF) signed by the patient or their legal representative, and follows the research protocol and follow-up process.

You may not qualify if:

• Acute promyelocytic leukemia (APL)；
• Malignant tumor in the past 2 years, except for cured localized skin cancer, superficial bladder cancer, cervical cancer or cancer in situ of breast cancer, and localized prostate cancer with Gleason score ≤ 6;
• Uncontrolled concurrent diseases, including but not limited to: ongoing or active uncontrolled infections, cardiovascular or mental illnesses/social situations that may limit compliance with research requirements;
• It is known that the subjects are positive for hepatitis B or hepatitis C infection, except those whose viral load cannot be detected within 3 months (Note: patients with HBcAb+but HBsAg - can only meet the condition if hepatitis B virus (HBV) DNA cannot be detected in the detection with sensitivity ≤ 20 IU/mL. In this case, patients should receive regular monitoring of HBV DNA and receive prophylactic antiviral drug treatment according to the central diagnosis and treatment routine; Patients with HCV antibody+are eligible only if they cannot detect HCV RNA and are willing to monitor HCV reactivation；
• Receive any moderate or strong CYP3A4 inhibitor (7 days or 5 half-lives, whichever is longer) or moderate or strong CYP3A4 inducer (14 days or 5 half-lives, whichever is longer) treatment before the first use of Sonrotoclax；
• Patients who are known to have hypersensitivity reactions to any component in the study protocol;
• Known central nervous system involvement in AML;
• Previously received organ, bone marrow, or peripheral blood organ transplantation；
• Participate in another therapeutic clinical study simultaneously；
• Pregnant or lactating women, or male and female patients planning to have children during the study period.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• Ruijin Hospital: collaborator
• BeiGene: collaborator

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

Location

Related Publications (1)

• Zhang Y, Wu M, Jin Z, Yang L, Huang X, Li W, Zhu H, Wang W, Chen Q, Liu L, Chen Z, Wang S, Li J. Risk-stratified treatment of sonrotoclax with chemotherapy in newly diagnosed acute myeloid leukemia: a study protocol. Future Oncol. 2025 Apr;21(8):953-958. doi: 10.1080/14796694.2025.2469487. Epub 2025 Feb 26.

  PMID: 40008672 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Idarubicin; Daunorubicin; Cytarabine; 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; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Ribonucleosides

Study Officials

• Junmin Li

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of hematology

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 11, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)