Combination treatment for newly diagnosed acute monocytic leukemia

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

This study is testing a new combination treatment for people with newly diagnosed acute monocytic leukemia who can't have intensive chemotherapy to see if it helps them feel better and manage their condition.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT05566054 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness and side effects of a combination treatment using venetoclax, azacitidine, and chidamide for patients with newly diagnosed acute monocytic leukemia (AML-M5) who are not eligible for intensive chemotherapy. The approach aims to address the challenges posed by resistance to venetoclax due to high levels of the anti-apoptotic protein MCL1, which is prevalent in AML-M5. By incorporating chidamide, a selective histone deacetylase inhibitor, the study seeks to enhance the therapeutic efficacy of the treatment regimen. The trial will evaluate both the clinical outcomes and safety profiles of this novel combination therapy.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with newly diagnosed acute monocytic leukemia (AML-M5) who are ineligible for intensive chemotherapy due to age or comorbidities.

Not a fit: Patients who are eligible for intensive chemotherapy or those with other types of leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with acute monocytic leukemia who cannot undergo intensive chemotherapy.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating acute myeloid leukemia, indicating potential for success in this approach.

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

Where this trial is running

Suzhou, Jiangsu

• The First Affliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Sheng-Li Xue, M. D.

Conditions Acute Monocytic Leukemia; Newly Diagnosed; Chidamide; Azacitidine; Venetoclax