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CAV Regimen for R/R AML

Primary Purpose

Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CAV Regimen
MEC Regimen
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring venetoclax, cladribine, cytarabine, relapsed/refractory AML

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Aged 16-65 years old. Diagnosed with R/R AML. 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: Patients who are allergic to the study drug or drugs with similar chemical structures. Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception. Active infection. Active bleeding. Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment. Patients with mental disorders or other conditions. 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). 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. Patients who relapsed after allogeneic hematopoietic stem cell transplantation. Drug abuse or long-term alcohol abuse that would affect the evaluation results. Patients who have received organ transplants. Patients not suitable for the study according to the investigator's assessment.

Sites / Locations

  • The First Affliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CAV regimen

MEC regimen

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
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)
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)
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)
Death due to treatment (within 8 weeks) during and after completion of chemotherapy.
Adverse events (AEs)
It is evaluated and graded according to CTCAE 5.0.

Full Information

First Posted
December 12, 2022
Last Updated
December 22, 2022
Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT05657639
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
venetoclax, cladribine, cytarabine, relapsed/refractory AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAV regimen
Arm Type
Experimental
Arm Title
MEC regimen
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
CAV Regimen
Intervention Description
Cladribine 5 mg/m2/day , cytarabine 20mg q12h, venetoclax 100mg d1, 200 d2, 400 mg/day from day 3 to day 21.
Intervention Type
Drug
Intervention Name(s)
MEC Regimen
Intervention Description
Mitoxantrone 8mg/m2 d1-5, etoposide 100mg/m2 d1-5, cytarabine 1g/m2 d1-5
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The overall response (completed remission, completed remission with incomplete blood count recovery, morphologic leukemia-free state and partial remission)
Time Frame
ORR assessment is measured on days 21 from the start of CAV regimen
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
2 years
Title
Event-free survival (EFS)
Description
EFS is measured from the time of enrollment to this study to treatment failure or relapse or any cause of death.
Time Frame
2 years
Title
Treatment-related mortality (TRM)
Description
Death due to treatment (within 8 weeks) during and after completion of chemotherapy.
Time Frame
2 months
Title
Adverse events (AEs)
Description
It is evaluated and graded according to CTCAE 5.0.
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 16-65 years old. Diagnosed with R/R AML. 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: Patients who are allergic to the study drug or drugs with similar chemical structures. Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception. Active infection. Active bleeding. Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment. Patients with mental disorders or other conditions. 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). 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. Patients who relapsed after allogeneic hematopoietic stem cell transplantation. Drug abuse or long-term alcohol abuse that would affect the evaluation results. Patients who have received organ transplants. Patients not suitable for the study according to the investigator's assessment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sheng-Li Xue, M. D.
Phone
008651267781139
Email
slxue@suda.edu.cn
Facility Information:
Facility Name
The First Affliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-Li Xue, M.D.
Phone
+86 512 6778 1139
Email
slxue@suda.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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CAV Regimen for R/R AML

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