Trial Title:
Phase II Study of Sonrotoclax Combined With Chemotherapy in the Treatment of Newly Diagnosed Acute Myeloid Leukemia
NCT ID:
NCT06497062
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Azacitidine
Daunorubicin
Idarubicin
Conditions: Keywords:
Sonrotoclax
Risk-stratified
Acute myeloid leukemia
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
sonrotoclax
Description:
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.
Arm group label:
Assigned Interventions
Other name:
BGB11417
Intervention type:
Drug
Intervention name:
idarubicin/daunorubicin
Description:
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
Arm group label:
Assigned Interventions
Other name:
IDA/DNR
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
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).
Arm group label:
Assigned Interventions
Other name:
Ara-c
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
75 mg/m^2, subcutaneously, once daily, on D1-7
Arm group label:
Assigned Interventions
Other name:
AZA
Intervention type:
Procedure
Intervention name:
allo-HSCT
Description:
Per standard of procedure
Arm group label:
Assigned Interventions
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.
Detailed description:
47 subjects who meet the eligibility criteria will receive no more than 2 cycles (each
cycle is 28 days) of induction therapy with sonrotoclax on day5-14 combined with the
standard 3+7 intensive chemotherapy regimen (3+7 regimen) containing cytarabine, and
daunorubicin or idarubicin. In cycle(C)1 of induction therapy, sonrotoclax will be
administered orally once daily by a 4-day dose rump-up of 20mg on Day(D)5, 40mg on D6,
80mg on D7, and 160mg on D8-14. The first 6 subjects will be enrolled in a Safety Run-in
period in C1 to assess tolerability and determine the final sonrotoclax regimen. Within
42 days or before the next cycle of therapy, if ≤1 of 6 subjects has dose-limiting
toxicities (DLT), the study will be continued with the sonrotoclax dose regimen as above,
and if ≥2 of 6 subjects have DLTs, the dose will be adjusted. Adjustment may include
reducing the dose, shortening the duration of each cycle, or terminating the study, based
on the DLTs' characteristics.
Subjects who achieve a composite complete remission (CRc) after induction therapy will
receive further consolidation therapy, which regimen will be decided based on the ELN
risk at diagnosis and MRD status detected by MFC after induction therapy.
After consolidation, subjects will receive once daily sonrotoclax orally combined with
azacitidine (AZA) subcutaneously once daily alternating with AZA monotherapy every 2
cycles as maintenance therapy until unacceptable toxicity, 12 months, recurrence, death,
withdrawal of informed consent, or study termination determined by investigators.
This single-armed study aims to investigate the safety and efficacy of a risk-stratified
regimen of sonrotoclax in combination with intensive chemotherapy in subjects with newly
diagnosed AML.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Newly diagnosed untreated acute myeloid leukemia patients;
2. Age range from 18 to 75 years old;
3. The Eastern Cooperative oncology Group (ECOG) score is ≤ 2 points;
4. 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%)
5. 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
6. 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.
7. 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.
8. 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.
9. The expected lifespan is greater than 12 weeks.
Exclusion Criteria:
1. Acute promyelocytic leukemia (APL)；
2. 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;
3. 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;
4. 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；
5. 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；
6. Patients who are known to have hypersensitivity reactions to any component in the
study protocol;
7. Known central nervous system involvement in AML;
8. Previously received organ, bone marrow, or peripheral blood organ transplantation；
9. Participate in another therapeutic clinical study simultaneously；
10. Pregnant or lactating women, or male and female patients planning to have children
during the study period.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Address:
City:
Shanghai
Country:
China
Contact:
Last name:
Junmin Li
Phone:
+86-021-64370045
Email:
drlijunmin@126.com
Start date:
September 4, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
Shanghai Jiao Tong University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Ruijin Hospital
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Source:
Shanghai Jiao Tong University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06497062
