Acute myeloid leukemia
Conditions
Interventions
Phase Ib trial group:QL1706 combined with azacitidine and venetoclax
QL1706: Corresponding dose in the assigned dose group (4/5 mg/kg), IV, d1, d14
Azacitidine (AZA): 75 mg/m2, subcutaneous injection, d1-d7
Venetoclax: 100 mg, orally, d1
200 mg, orally, d2
400 mg, orally, d3-d28.
Phase II trial group: Cohort A:QL1706
QL1706: RP2D (determined based on Phase Ib), IV, d1, d14
Phase II trial group: Cohort B:QL1706
QL1706: RP2D (determined based on Phase Ib), IV, d1, d14
Sponsors
Sun Yat-Sen University Cancer Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of AML , excluding APL, confirmed according to the WHO 2016 diagnostic criteria for AML; 2. Age >=18 years, regardless of gender; 3. Subjects must meet at least one of the following conditions: (1) Elderly AML subjects inclusion criteria: According to the WHO 2016 diagnostic criteria for AML, newly diagnosed with AML (excluding APL), age >=60 years, and have adequate organ function: liver and kidney function, cardiac and pulmonary function meeting the following requirements within 2 weeks prior to enrollment: 1) Creatinine =45%; 3) Oxygen saturation >91%; 4) Total bilirubin =30 ml/min and 3 times the normal value) and age >=60 years, or any cholangiocarcinoma, or uncontrolled liver cancer or acute viral hepatitis, or total bilirubin >1.5 ULN and =5% (excluding other causes such as bone marrow regeneration after consolidation chemotherapy), or extramedullary leukemia cell infiltration. (4) Diagnostic criteria for refractory AML: Newly diagnosed cases ineffective after two courses of standard therapy; Relapse within 12 months after CR and consolidation/intensive therapy; Relapse after 12 months and ineffective after conventional chemotherapy; Two or more relapses; Persistent extramedullary leukemia. 4. Pre-treatment bone marrow CD3+ T cells >=13.2% or peripheral blood CD3+ T cells >=20.5%; 5. Expected survival time exceeding 3 months; 6. Women of childbearing potential must agree to use contraception during the study and for 3 months after study completion; have a negative serum pregnancy test within 7 days before study enrollment, and must be non-lactating; men must agree to use contraception during the study and for 3 months after study completion; 7. Voluntarily participate in the clinical study, sign the informed consent form, and be willing and able to comply with all trial procedures.
Exclusion criteria
Exclusion criteria: 1. Known allergy to PD1/CTLA4 combination antibody drug analogues; 2. Concurrently receiving other targeted therapies for AML, such as dasatinib, sorafenib, gilteritinib, midostaurin, etc.; 3. Previous treatment targeting PD1/CTLA4 and experienced disease progression during such therapy; 4. Presence of any severe complications (e.g., interstitial lung disease, organ dysfunction, etc.) or concomitant diseases (e.g., uncontrolled diabetes, autoimmune diseases, etc.) or active major bleeding in visceral organs (including gastrointestinal bleeding, alveolar hemorrhage, intracranial hemorrhage, etc.); (This criterion does not apply to the screening for enrollment of patients aged <60 years but classified as AML patients intolerant to intensive chemotherapy (unfit-AML)); 5. For relapsed/refractory AML subjects, exposure to azacitidine and venetoclax is allowed, but relapsed/refractory AML patients with prior progression on venetoclax and azacitidine are excluded; 6. Any other situation deemed by the investigator as unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite Complete Remission Rate;Recommended Phase II Dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Minimal Residual Disease Negative Conversion Rate;Adverse Events;Time to Complete Remission;Overall Response Rate;Duration of Response;Progression-Free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactLiang Yang
Sun Yat-sen University Cancer Center
Outcome results
None listed