CAV Regimen for R/R Ph- B-ALL

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

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: cladribine, cytarabine,venetoclax

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Sheng-Li Xue, M.D.; Phone Number: +86 512 6778 1139; Email: slxue@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 15-70 years old.
2. Patients diagnosed with R/R Ph- B-ALL.
3. 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.
4. ECOG performance status score less than 2.
5. Expected survival time ≥ 12 weeks.
6. Patients 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 of 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. Surgery on the main organs within the past six weeks.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The Second People's Hospital of Huai'an; Jining Medical University; Affiliated Hospital of Nantong University; Suzhou Hospital of Traditional Chinese Medicine; Northern Jiangsu People's Hospital; The First Affiliated Hospital of Bengbu Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 21, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: venetoclax; cytarabine; cladribine; relapsed/refractory ALL
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Ribonucleosides; Arabinonucleosides; Deoxyribonucleosides; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Deoxyadenosines; Cytarabine; Cladribine; venetoclax
• Other Study ID Numbers: SZBALL01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No