Clinical trial NCT05657652: CAV Regimen for R/R Ph- B-ALL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Lymphoblastic Leukemia
Keywords: venetoclax
cladribine
cytarabine
relapsed/refractory ALL
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Jining Medical University
name: The Second People's Hospital of Huai'an
name: The First Affiliated Hospital of Bengbu Medical University
name: Northern Jiangsu People's Hospital
name: Affiliated Hospital of Nantong University
name: Suzhou Hospital of Traditional Chinese Medicine
First posted: 2022-12-20
Enrollment: 36
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: ORR assessment is measured on days 21 from the start of CAV regimen
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Progression-Free Survival (PFS)
timeFrame: 2 years
measure: Adverse events
timeFrame: 1 month
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: