Clinical trial NCT05662956: A Clinical Study of VA-CAG as Induction Therapy in Newly Diagnosed AML Patients
Official title: A Phase II Study to Evaluate the Safety and Efficacy of Venetoclax in Combination With Azacitidine and CAG(VA-CAG) as Induction Therapy in Newly Diagnosed Patients With Acute Myeloid Leukemia(AML)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Venetoclax
Azacitidine
Granulocyte colony-stimulating factor(G-CSF)
Cytarabine
Aclarubicin
Lead sponsor: Hematology department of the 920th hospital
Sponsor class: OTHER
First posted: 2022-12-23
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG(VA-CAG) as induction regimen in newly diagnosed young patients with acute myeloid leukemia(AML).

Detailed description: This is an open-label, multicenter, phase II clinical trial to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine (VA) and CAG (G-CSF priming, low dose cytarabine, and aclarubicin) as induction regimen in newly diagnosed patients with acute myeloid leukemia (AML).

The combination of venetoclax and azacitidine is the standard therapy for elderly (\> 60 year old) patients with newly diagnosed AML who are not eligible for intensive chemotherapy. Previous studies have shown that venetoclax plus intense chemotherapy represent promising efficacy in de novo AML patients with high complete remission rates and good tolerance. The preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for newly diagnosed young patients with AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 100 patients will take part in this trial.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥ 18 years old and ≤ 65 years old
2. Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification;
3. Patients without receiving prior therapy for AML;
4. Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3;
5. Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN
6. Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN
7. Heart function: left ventricular ejection fraction ≧45%
8. Patients must participate in this clinical trial voluntarily and sign an informed consent form.

Exclusion Criteria:

1. Acute promyeloid leukemia；
2. AML with central nervous system (CNS) infiltration；
3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
4. Patients with a life expectancy \<3 months
5. Patients with uncontrolled active infection;
6. HIV infection;
7. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; b) An active second cancer that requires treatment within 6 months of study entry.
8. Female who are pregnant, breast feeding or childbearing potential.
9. Patients deemed unsuitable for enrollment by the investigator.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: At the end of Cycle 1 and Cycle 2 of induction(each cycle is 28 days)
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (>=grade 3 )
timeFrame: Up to 2 years
measure: Duration of myelosuppression
timeFrame: Up to 2 years
measure: Leukaemia-free survival
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: Up to 2 years
measure: Rate of Minimal Residual Disease (MRD) negativity
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
state: Yunnan
Study officials:
affiliation: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: