Clinical trial NCT05433532: Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
Official title: A Phase Ⅱ, Open Label, Single Arm, Single-Center Study to Evaluate the Efficacy and Safety of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Philadelphia Chromosome
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Chronic Myeloid Leukemia
Mixed Phenotype Acute Leukemia
Keywords: Ph-positive AL
CML-AP/BP
Azacitidine+Venetoclax+Flumatinib
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2022-06-27
Enrollment: 20
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: The purpose of this study is to evaluate the efficacy and safety of azacitidine，venetoclax，and flumatinib in newly diagnosed Philadelphia chromosome-positive acute leukemia and accelerated phase or blast phase chronic myeloid leukemia patients.

Detailed description: This is a phase Ⅱ, open-label, single-arm, single-center study in newly diagnosed Ph-positive acute leukemia and CML-AP/BP patients. The patients will receive azacitidine, venetoclax, and flumatinib regimen in the induction treatment. The patients who respond to induction treatment will undergo consolidation treatment, and an optional allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment with induction therapy according to patient's wishes.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed Ph-positive ALL/AML/MPAL and CML-AP/BP without the history of chemotherapy or target therapy.
2. Age 18-65.
3. Eastern Cooperative Oncology Group (ECOG) score: 0-3.
4. Total serum bilirubin ≤ 2 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 1.5 x ULN, aspartate aminotransferase (AST) ≤ 1.5 x ULN.
5. Creatinine clearance ≥ 30 mL/min.
6. Serum lipase ≤ 1.5 x ULN, amylase =\< 1.5 x ULN.
7. No consumption of grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax.
8. Provide informed consent.

Exclusion Criteria:

1. Patients with another malignant disease.
2. Patients has participated in or participating in other clinical trials.
3. Patients with uncontrolled active infection.
4. Patients with left ventricular ejection fraction \< 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
5. Patients with HIV infection, active tuberculosis infection, or active hepatitis B or hepatitis C infection.
6. Patients with uncontrolled active bleeding.
7. Patients with history of previous chemotherapy or target therapy (except for oral hydroxyurea and/or leukopheresis for lowering white blood cell counts).
8. Pregnant and lactating women; patients of childbearing potential should be willing to practice methods of contraception throughout the study period.
9. Patients with other commodities that the investigators considered not suitable for the enrollment.

Primary outcomes:
measure: CMR
timeFrame: End of cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: CR/CRi, MRD-negative CR, CCyR, MMR
timeFrame: End of cycle 1 and 2 (each cycle is 28 days)
measure: Number of adverse events
timeFrame: End of cycle 1 and 2 (each cycle is 28 days)
measure: RFS
timeFrame: 2 years
measure: OS
timeFrame: 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Xiaowen Tang, Ph.D
role: STUDY_CHAIR
References: