Clinical trial NCT05657639: CAV Regimen for R/R AML
Official title: Venetoclax, Cladribine Plus Low-dose Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: venetoclax
cladribine
cytarabine
relapsed/refractory AML
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: 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: Jining Medical University
name: The First People's Hospital of Changzhou
name: The First Affiliated Hospital of Anhui Medical University
name: First Affiliated Hospital of Zhejiang University
name: YANCHENG NO.1 PEOPLE'S HOSPITAL
name: Kaifeng Central Hospital
First posted: 2022-12-20
Enrollment: 68
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the efficacy and safety of cladribine, combined with low-dose cytarabine and venetoclax (CAV regimen) for relapsed/refractory acute myeloid leukemia (R/R AML).

Detailed description: Patients with relapse/refractory (R/R) acute myeloid leukemia often show resistance to conventional chemotherapy and have dismal prognosis. Salvage therapy using venetoclax combined with hypomethylation drugs achieved an overall response rate of only approximately 40% in R/R AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells.The efficacy of cladribine plus cytarabine and venetoclax in R/R AML has not been reported.

Eligibility criteria: Inclusion Criteria:

1. Aged 16-70 years old.
2. Diagnosed with R/R AML.
3. Patients with AML must meet one of the following criteria, A or B: A: Refractory AML disease was defined as follows: (1) failure to attain CR following exposure to at least 2 courses of standard or intensive induction therapy; or (2) bone marrow leukemia cell decline index (BMCDI) \< 50% and \> 20% after 1 course of standard or intensive induction therapy. B: Relapsed AML disease was defined as follows:

(1) reappearance of leukemic blasts in the peripheral blood after CR; or (2) detection of ≥ 5% blasts in the BM not attributable to another cause (e.g., BM regeneration after consolidation therapy); or (3) extramedullary relapse.

4. ECOG performance status score less than 2. 5. Expected survival time ≥12 weeks. 6. Without serious heart, lung, liver, or kidney dysfunction. 7. Able to understand and provide informed consent.

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.
7. Liver function abnormalities (total bilirubin \> 1.5 times of the upper limit of the normal range, ALT/AST \> 2.5 times of 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 dysfunction (Ccr\<50ml/h).
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. Patients who relapsed after allogeneic hematopoietic stem cell transplantation.
10. Drug abuse or long-term alcohol abuse that would affect the evaluation results.
11. Patients who have received organ transplants.
12. Patients not suitable for the study according to the investigator's assessment.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: ORR assessment is measured on days 21 from the start of CAV regimen
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Event-free survival (EFS)
timeFrame: 2 years
measure: Treatment-related mortality (TRM)
timeFrame: 2 months
measure: Adverse events (AEs)
timeFrame: 2 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: