CAV Regimen for R/R AML
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: CAV regimen
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Drug: CAV Regimen
Cladribine 5 mg/m2/day , cytarabine 20mg q12h, venetoclax 100mg d1, 200 d2, 400 mg/day from day 3 to day 21.
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Active Comparator: MEC regimen
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Drug: MEC Regimen
Mitoxantrone 8mg/m2 d1-5, etoposide 100mg/m2 d1-5, cytarabine 1g/m2 d1-5
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Outcome Measures
Primary Outcome Measures
- Overall response rate (ORR) [ORR assessment is measured on days 21 from the start of CAV regimen]
The overall response (completed remission, completed remission with incomplete blood count recovery, morphologic leukemia-free state and partial remission)
Secondary Outcome Measures
- Overall Survival (OS) [2 years]
OS is measured from the time of enrollment to this study to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
- Event-free survival (EFS) [2 years]
EFS is measured from the time of enrollment to this study to treatment failure or relapse or any cause of death.
- Treatment-related mortality (TRM) [2 months]
Death due to treatment (within 8 weeks) during and after completion of chemotherapy.
- Adverse events (AEs) [2 months]
It is evaluated and graded according to CTCAE 5.0.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 16-65 years old.
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Diagnosed with R/R AML.
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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.
- 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:
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Patients who are allergic to the study drug or drugs with similar chemical structures.
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Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception.
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Active infection.
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Active bleeding.
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Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment.
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Patients with mental disorders or other conditions.
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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).
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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.
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Patients who relapsed after allogeneic hematopoietic stem cell transplantation.
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Drug abuse or long-term alcohol abuse that would affect the evaluation results.
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Patients who have received organ transplants.
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Patients not suitable for the study according to the investigator's assessment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The First Affliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- The Second People's Hospital of Huai'an
- First Affiliated Hospital Bengbu Medical College
- Northern Jiangsu Province People's Hospital
- Affiliated Hospital of Nantong University
- Suzhou Hospital of Traditional Chinese Medicine
- Jining Medical University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SZAML02