CAV Regimen for R/R AML

Sponsor
The First Affiliated Hospital of Soochow University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05657639
Collaborator
The Second People's Hospital of Huai'an (Other), First Affiliated Hospital Bengbu Medical College (Other), Northern Jiangsu Province People's Hospital (Other), Affiliated Hospital of Nantong University (Other), Suzhou Hospital of Traditional Chinese Medicine (Other), Jining Medical University (Other)
68
1
2
24
2.8

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
  • Drug: CAV Regimen
  • Drug: MEC Regimen
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

Study Type:
Interventional
Anticipated Enrollment :
68 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Venetoclax, Cladribine Plus Low-dose Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, Randomized, Controlled Study
Actual Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Oct 1, 2024
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: CAV regimen

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.

Active Comparator: MEC regimen

Drug: MEC Regimen
Mitoxantrone 8mg/m2 d1-5, etoposide 100mg/m2 d1-5, cytarabine 1g/m2 d1-5

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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.

  3. Treatment-related mortality (TRM) [2 months]

    Death due to treatment (within 8 weeks) during and after completion of chemotherapy.

  4. Adverse events (AEs) [2 months]

    It is evaluated and graded according to CTCAE 5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:
16 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Aged 16-65 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.

  1. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Sheng-Li Xue, MD, Professor, The First Affiliated Hospital of Soochow University
ClinicalTrials.gov Identifier:
NCT05657639
Other Study ID Numbers:
  • SZAML02
First Posted:
Dec 20, 2022
Last Update Posted:
Dec 27, 2022
Last Verified:
Dec 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Sheng-Li Xue, MD, Professor, The First Affiliated Hospital of Soochow University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 27, 2022