CAV Regimen for R/R Ph- B-ALL

Study Overview
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Brief Summary
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This study aims to investigate the efficacy and safety of cladribine, venetoclax combined with cytarabine and venetoclax (CAV regimen) for relapsed/refractory (R/R) Philadelphia Chromosome-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL).

Detailed Description
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Relapse is common in Ph- B-ALL and a proportion of patients present refractory to initial treatment. Treatments for these patients consist immunotherapy and conventional chemotherapy. The former is too expensive and the latter has a low remission rate. Treatment for R/R Ph- B-ALL still remains a challenge. The efficacy and safety of cladribine, venetoclax and cytarabine (CAV) has not been explored in ALL. Thus investigators design such a clinical trial to investigate the efficacy and safety of CAV regimen for R/R Ph- B-ALL.

Official Title
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Venetoclax, Cladribine Plus Low-dose Cytarabine for Relapsed/Refractory Philadelphia Chromosome-negative (Ph-) B-cell Acute Lymphoblastic Leukemia (B-ALL): a Single-arm, Multicenter Study

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: cladribine, cytarabine,venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 13-65 years old. Patients diagnosed with R/R Ph- B-ALL. Patients with ALL must meet one of the following criteria, A or B: A: Refractory ALL disease was defined as follows: (1) failure to attain CR following exposure to at least 1 courses of standard induction therapy; B: Relapsed ALL 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. Expected survival time ≥ 12 weeks. Patients without serious heart, lung, liver, or kidney dysfunction. 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 of 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. Surgery on the main organs within the past six weeks. 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.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAV regimen<br> | Drug: cladribine, cytarabine,venetoclax<br>* Cladribine 5 mg/m2/day, cytarabine 20mg q12h, venetoclax 100mg d1, 200 d2, 400 mg/day from day 3 to day 21.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The overall response (completed remission, completed remission with incomplete blood count recovery) | ORR assessment is measured on days 21 from the start of CAV regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is measured from the time of enrollment to this trial 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 years | 
| Progression-Free Survival (PFS) | PFS is measured from the time of enrollment to this study to progression or death. | 2 years | 
| Adverse events | It is evaluated and graded according to CTCAE 5.0. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venetoclax, cladribine, cytarabine, relapsed/refractory ALL