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

December 23, 2024 updated by: First Affiliated Hospital of Zhejiang University

Venetoclax Combined With Olverembatinib and Predinisone in Treating Ph-positive Precursor B Cell Acute Lymphoblastic Leukemia: a Phase II, Single Arm and Multicenter Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Recruiting
        • The first Affiliated Hospital, Zhejiang University School of Medicine
        • Principal Investigator:
          • Jie Jin, M.D.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm

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.
Drug: Venetoclax
BCL-2 inhibotor
Other Names:
  • Ven
Drug: Olverembatinib
Tyrosine kinase inhibitor
Other Names:
  • Olv
Drug: Predinisone
Glucocorticoids

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission with or without incomplete PB cell recovery(CR/CRi) rate
Time Frame: after Cycle 1(each cycle is 28 days)
Blast rate lower than 5% with or without peripheral blood cell recover
after Cycle 1(each cycle is 28 days)
Event free survival (EFS)
Time Frame: 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;
up to 2 years
Overall survival (OS)
Time Frame: 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;
up to 2 years
Minimal residual disease (MRD)
Time Frame: 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
At the end of each cycle（each cycle is 28 days）, up to 2 years
Relapse free survival(RFS)
Time Frame: 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;
up to 2 years
Incidence of Adverse Events
Time Frame: 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.
From day 1 of treatment to 28 days after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Zhejiang University

Investigators

  • Principal Investigator: Jie Jin, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

December 30, 2025

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

December 18, 2024

First Submitted That Met QC Criteria

December 23, 2024

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 23, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT20240094C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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