Clinical trial NCT05566054: Venetoclax and Azacitidine Combined With Chidamide (VAC) for the Treatment of Newly Diagnosed Acute Monocytic Leukemia
Official title: A Multicenter, Randomized, Controlled Clinical Trial of Venetoclax, Azacytidine Combined With Chidamide for the Treatment of Newly Diagnosed Acute Monocytic Leukemia Patients That Are Ineligible for Intensive Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Monocytic Leukemia
Newly Diagnosed
Keywords: Chidamide
Azacitidine
Venetoclax
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Jining Medical University
name: The Second People's Hospital of Huai'an
name: The First Affiliated Hospital of Bengbu Medical University
name: Northern Jiangsu People's Hospital
name: Affiliated Hospital of Nantong University
name: Suzhou Hospital of Traditional Chinese Medicine
name: Taizhou University
First posted: 2022-10-04
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to investigate the therapeutic efficacy and side effect of venetoclax, azacytidine combined with chidamide for newly diagnosed acute monocytic leukemia patients that are ineligible for intensive chemotherapy

Detailed description: Acute myeloid leukemia (AML) is one of the most aggressive blood cancers, with a very low survival rate and few options for patients who are unable to undergo intensive chemotherapy. Venetoclax in combination with hypomethylation agents or cytarabine has been approved by the Food and Drug Administration (FDA) for the treatment of patients with newly diagnosed AML unfit for intensive chemotherapy. However, resistance to venetoclax can be acquired through the upregulation of anti-apoptotic proteins in the BCL2 family, such as myeloid cell leukaemia 1 (MCL1). MCL1 plays a critical role in cell apoptosis regulation and high expression of MCL1 is observed in acute monocytic leukemia (AML-M5) . Chidamide, a newly designed selective histone deacetylase inhibitor, resulted in a decrease in the protein level of MCL1. This study is to investigate the therapeutic efficacy and side effect of venetoclax, azacytidine combined with chidamide for newly diagnosed AML-M5 patients that are ineligible for intensive chemotherapy.

Eligibility criteria: Inclusion Criteria:

Confirmation of acute monocytic leukemia( AML-M5) diagnosis by the French-American-British (FAB) Classification and/or characterized for expression of monocytic and myeloid differentiation markers, have a projected life expectancy of at least 12 weeks, previously untreated, and ineligible for treatment with intensive chemotherapy.

Patients must be considered ineligible for induction therapy defined by the following:

1. \>= 60 years of age
2. \>=18 to 59years of age with at least one of the following comorbidities:

   Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy:

   (A)Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3. (B)Cardiac history of congestive heart failure requiring treatment or ejection fraction \<= 50% or chronic stable angina.

   (C)Diffusing capacity of the lung for carbon monoxide (DLCO) \<= 65% or forced expiratory volume during the first second (FEV1) \<= 65%.

   (D)Creatinine clearance \>= 30 mL/min to \< 45 mL/min. (E)Moderate hepatic impairment with total bilirubin \> 1.5 to \<= 3.0 × upper limit of normal (ULN).
3. Must meet the laboratory requirements per the protocol.
4. Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study or for approximately 90 days after the last dose of study drug.
5. Female participants of childbearing potential must agree to use at least 1 protocol-specified method of birth control and male participants, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.
6. Did not receive radiotherapy, chemotherapy, targeted therapy or hematopoietic stem cell transplantation within 4 weeks before enrollment;
7. Other comorbidities that are not suitable for intensive chemotherapy;
8. The patient refused to receive intensive chemotherapy;
9. Ability to understand and willing to sign the informed consent for this trial.

Exclusion Criteria:

1. Patients who are allergic to the study drug or drugs with similar chemical structures
2. Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception
3. Active infection
4. Active bleeding
5. Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment
6. Patients with mental disorders or other conditions whereby informed consent cannot be obtained and where the requirements of the study treatment and procedures cannot be met
7. Liver function abnormalities (total bilirubin \> 1.5 times the upper limit of the normal range, ALT/AST \> 2.5 times the upper limit of the normal range or patients with liver involvement whose ALT/AST \> 1.5 times the upper limit of the normal range), or renal anomalies (serum creatinine \> 1.5 times the upper limit of the normal value)
8. Patients with a history of clinically significant QTc interval prolongation (male \> 450 ms; female \> 470 ms), ventricular heart tachycardia and atrial fibrillation, II-degree heart block, myocardial infarction attack within one year before enrollment, and congestive heart failure, and patients with coronary heart disease who have clinical symptoms and requiring drug treatment
9. Urgery on the main organs within the past six weeks
10. Drug abuse or long-term alcohol abuse that would affect the evaluation results
11. Patients who have received organ transplants (excepting bone marrow transplantation)
12. Patients not suitable for the study according to the investigator's assessment

Primary outcomes:
measure: Composite Complete Remission Rate
timeFrame: At the end of Cycle 1 or 2 (each cycle is 28 days)
measure: Overall response rate (ORR)
timeFrame: At the end of Cycle 1 or 2 (each cycle is 28 days)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Progression-Free Survival (PFS)
timeFrame: 1 year
measure: Adverse reactions in hematology
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Nonhematological adverse reactions
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: