Clinical trial NCT06754267: Venetoclax Combined With Olverembatinib and Predinisone in Treating Ph+ B-ALL
Official title: Venetoclax Combined With Olverembatinib and Predinisone in Treating Ph-positive Precursor B Cell Acute Lymphoblastic Leukemia: a Phase II, Single Arm and Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Precursor B-Cell Acute Lymphoblastic Leukemia
Keywords: acute lymphoblastic leukemia
Ph chromosome
BCL2 inhibitor
TKI
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2024-12-31
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive type of leukemia, with high relapse rate and poor long term survival in adults. Philadelphia chromosome positive (Ph+) ALL is defined as ALL with translocation between chromosomes 9 and 22. And t(9;22)(q34;q11) is the most common chromosomal abnormality in ALL. Before the emergence of TKI, the prognosis of Ph+ ALL was extremely poor, and the long-term survival rate was only 10%-35%. Ph+ ALL accounts for about 30% of adult ALL. In this study, the investigators propose a treatment approach that combines Venetoclax with Olverembatinib and Predinisone in Ph+ B-ALL adults. The study aims to answer the safety and efficacy of this treatment regimen, and further improve the survival for those participants.

Detailed description: This is a prospective, single-arm, phase II and open-label study. A total of 36 Ph-positive B-ALL participants will be enrolled. The primary endpoint is complete molecular response (CMR) after three cycles of venetoclax combined with olverembatinib and prednisone regimen (VOP) in the treatment of de novo acute Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia. The purpose of this study is to explore the safety and efficacy of the multi-drug combination regimen in the treatment of newly diagnosed Ph-positive B-ALL patients.

Eligibility criteria: Inclusion Criteria:

1. Before enrollment, the patient must be diagnosed with de novo precursor B-cell acute lymphoblastic leukemia and positive for Philadelphia chromosome (presence of t(9;22) and/or BCR::ABL1 positive and/or FISH positive). The diagnostic criteria refer to the 2022 WHO classification;
2. Age ≥ 18 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
4. Expected survival time ≥ 3 months;
5. No organ dysfunction that would restrict the use of this protocol during the screening period;
6. Understand the study and sign the informed consent form.
7. Men, women of childbearing age (only postmenopausal women who have been menopausal for at least 12 months can be considered infertile), and their partners voluntarily take effective contraceptive measures deemed effective by the investigator during the treatment period and for at least 12 months after the last dose of the study drug.

Exclusion Criteria:

1. Accelerated phase or blast crisis of chronic myeloid leukemia;
2. Subjects with involvement of the central nervous system (CNS) or accompanied by extramedullary lesions;
3. Subjects who have received systemic anti-leukemia treatment (including but not limited to TKI, radiotherapy or chemotherapy, except for the allowed pretreatment);
4. Subjects with a history of myocardial infarction within 12 months, or have clinical manifestations of heart disease (including but not limited to unstable angina pectoris, congestive heart failure, uncontrolled hypertension and uncontrolled arrhythmia, etc.); left ventricular ejection fraction (LVEF) on echocardiography \<50%;
5. Diseases with abnormal functions of organs such as lung, liver, and kidney that may limit the patient's participation in this trial (including but not limited to severe infection, uncontrolled diabetes, active tuberculosis, asthma, COPD, bronchiectasis, etc.);
6. History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer;
7. Serum total bilirubin \> 1.5 ULN (upper limit of normal); ALT or AST \> 2.5 ULN; serum creatinine \> 1.5 ULN;
8. Known HIV infection;
9. Conditions affecting the use of the study drug as assessed by the investigator;
10. Unable to understand or comply with the study protocol.

Primary outcomes:
measure: complete molecular response (CMR) after three cycles
timeFrame: At the end of Cycle 3（each cycle is 28 days）
Secondary outcomes:
measure: Complete remission with or without incomplete PB cell recovery(CR/CRi) rate
timeFrame: after Cycle 1(each cycle is 28 days)
measure: Event free survival (EFS)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
measure: Minimal residual disease (MRD)
timeFrame: At the end of each cycle（each cycle is 28 days）, up to 2 years
measure: Relapse free survival(RFS)
timeFrame: up to 2 years
measure: Incidence of Adverse Events
timeFrame: From day 1 of treatment to 28 days after the last dose
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Jie Jin
role: PRINCIPAL_INVESTIGATOR
References:
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