Clinical trial NCT05918198: Clinical Study of Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia
Official title: Clinical Study of BCL-2 Inhibitor Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2023-06-26
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the safety and efficacy of venetoclax plus CAG regimen in refractory/relapsed acute myeloid leukemia patients.

Detailed description: The main questions it aims to answer are:

* Safety of Ven combined with CAG regimen in the treatment of relapsed/refractory AML patients
* Efficacy of Ven combined with CAG regimen in the treatment of relapsed/refractory AML patients Participants will receive therapy of venetoclax and CAG regimen (Ara-C, Acla and C C-GSF)

Eligibility criteria: Inclusion Criteria:

* 18 years ≤ age ≤ 75 years, male and female are not limited.
* According to bone marrow morphology and immunophenotype, it was diagnosed as acute myeloid leukemia ( WHO 2016 diagnostic criteria).
* Morphological recurrence after complete remission (CR) (leukemic cells in the peripheral blood of CR patients or more than 5% of the blasts in the bone marrow or new pathological hematopoiesis or extramedullary leukemic cell infiltration) or acute myeloid leukemia patients who did not achieved CR after 1 cycle of chemotherapy.
* The ECOG (Eastern Cancer Cooperation Group of the United States) PS score is 0-1.
* The expected survival time is ≥ 12 weeks.
* Female patients of childbearing age need to undergo pregnancy examination before receiving chemotherapy, and must agree to take effective contraceptive measures during treatment.
* Subjects volunteered to participate, fully informed consent, signed an informed consent, and good compliance.

Exclusion Criteria:

* Other malignant hematological diseases that do not conform to the diagnosis of acute myeloid leukemia.
* Allergy to any drugs involved in the project.
* History of serious cardiovascular and cerebrovascular diseases: ① Congestive heart failure, unstable angina pectoris, myocardial infarction, stroke or poorly controlled arrhythmia with NYHA grade II or above occurred within 12 months before enrollment，LVEF (left ventricular ejection fraction)\<50% by color Doppler ultrasound，Corrected QT interval (QTc)\>480ms (calculated by Fridericia method, if the QTc is abnormal, it can be detected continuously for 3 times every 2 minutes, and the average value is taken)，Hypertension difficult to control by drugs (systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg) (based on the average of ≥ 3 BP readings obtained from ≥ 2 measurements)，Have had hypertensive crisis or hypertensive encephalopathy in the past.
* There are other obvious bleeding tendencies or evidence of major coagulation disorders: ①Hemoptysis of any reason occurred within 2 weeks before enrollment，② Thrombosis or embolism occurred within 6 months before enrollment，③ Anticoagulant therapy for therapeutic purposes (except low molecular weight heparin therapy) be used within 2 weeks before enrollment④ Antiplatelet therapy is required.
* Abnormal liver function: total bilirubin\>3 mg/dL；Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 5 × Upper limit of normal value (ULN).
* Abnormal renal function: serum creatinine ≥ 1.5 × ULN, or the creatinine clearance rate (CrCl) calculated according to Cockroft-Gault formula is less than 60 mL/min (if the calculated CrCl is less than 60 mL/min, the researcher may ask to confirm the 24-hour CrCl, in this case, the subjects with 24-hour CrCl less than 60 mL/min should be excluded).
* Other serious diseases that may limit the patient's participation in this clinical trial (including but not limited to other malignant tumors, active infection, serious uncured wounds, active ulcers and untreated fractures, history of human immunodeficiency virus infection, and receiving allogeneic stem cells or solid organ transplantation).
* Cannot swallow pills, malabsorption syndrome or any condition that affects gastrointestinal absorption.
* Other clinical trials are being conducted.
* Unable to understand or cooperate to complete the research protocol.
* Pregnant and lactating patients
* Other situations that the researcher believes are not suitable for inclusion in the study.

Primary outcomes:
measure: CR/CRi rate
timeFrame: 2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
measure: CR/CRi rate
timeFrame: 2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
Secondary outcomes:
measure: MRD status
timeFrame: 2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
measure: MRD status
timeFrame: 2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
measure: objective remission rate（ORR）
timeFrame: 2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
measure: objective remission rate（ORR）
timeFrame: 2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
measure: Progression-free survival (PFS)
timeFrame: Throughout the whole research process, assessed up to 24 months
measure: Overall survival
timeFrame: Throughout the whole research process, assessed up to 24 months
measure: The incidence of adverse events
timeFrame: Throughout the whole research process, assessed up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Wen-Jing Yu, M.D.
role: STUDY_CHAIR
References: