Venetoclax Combined With Olverembatinib and Predinisone in Treating Ph+ B-ALL

Phase 2

Recruiting

• Conditions: Precursor B-Cell Acute Lymphoblastic Leukemia
• Interventions: Drug: Venetoclax; Drug: Olverembatinib; Drug: Predinisone

• Registration Number: NCT06754267
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

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.

Study Timeline

• Status Verified: 2024-12
• Study Start: 2024-12
• Study First Submitted: 2024-12-18
• Study First Submitted QC: 2024-12-23
• Last Update Submitted: 2024-12-23
• Study First Posted: 2024-12-31
• Last Update Posted: 2024-12-31
• Primary Completion: 2025-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Venetoclax	Induction Cycle 1: Olverembatinib for 4 weeks, oral; Venetoclax for 4 weeks, oral; Predinisone for 3 weeks, oral. Consolidation Cycle 2 and 3: Olverembatinib for 4 weeks, oral; Venetoclax for 2 weeks, oral; Predinisone for 2 weeks, oral.
Treatment arm	Olverembatinib	Induction Cycle 1: Olverembatinib for 4 weeks, oral; Venetoclax for 4 weeks, oral; Predinisone for 3 weeks, oral. Consolidation Cycle 2 and 3: Olverembatinib for 4 weeks, oral; Venetoclax for 2 weeks, oral; Predinisone for 2 weeks, oral.
Treatment arm	Predinisone	Induction Cycle 1: Olverembatinib for 4 weeks, oral; Venetoclax for 4 weeks, oral; Predinisone for 3 weeks, oral. Consolidation Cycle 2 and 3: Olverembatinib for 4 weeks, oral; Venetoclax for 2 weeks, oral; Predinisone for 2 weeks, oral.

Primary Outcome Measures

Name	Time	Method
complete molecular response (CMR) after three cycles	At the end of Cycle 3（each cycle is 28 days）	BCR::ABL1≤0.01% detected by RT-qPCR

Secondary Outcome Measures

Name	Time	Method
Complete remission with or without incomplete PB cell recovery(CR/CRi) rate	after Cycle 1(each cycle is 28 days)	Blast rate lower than 5% with or without peripheral blood cell recover
Event free survival (EFS)	up to 2 years	Defined for all patients in a trial; measured from day 1 of treatment to the date of treatment failure, hematologic relapse from CR/CRi or death from any cause, whichever occurs first;
Overall survival (OS)	up to 2 years	Defined for all patients in a trial; measured from day 1 of treatment to the date of death from any cause;
Minimal residual disease (MRD)	At the end of each cycle（each cycle is 28 days）, up to 2 years	MRD level detected by flow cytometry which value \<0.1% is defined as negtive; MRD level detected by RT-qPCR which BCR::ABL1 value \<0.01% is defined as negtive
Relapse free survival(RFS)	up to 2 years	Defined only for patients achieving CR or CRi; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause;
Incidence of Adverse Events	From day 1 of treatment to 28 days after the last dose	The safety of the drug was evaluated by NCI-CTC AE 5.0 standard.Hematologic and non-hematologic toxicity.

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China