A Study of Olverembatinib in Patients With Newly Diagnosed Ph+ALL.

Study Overview
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Brief Summary
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A global multicenter, open-label, randomized and registrational Phase 3 study to evaluate efficacy and safety of Olverembatinib combined with chemotherapy versus Imatinib combined with chemotherapy in subjects with newly diagnosed Ph+ALL.

Detailed Description
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Comparing efficacy and safety of Olverembatinib in combination with chemotherapy (investigational arm) vs. Imatinib in combination with chemotherapy (control arm).

Official Title
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A Pivotal Registrational Phase 3 Study of Olverembatinib Combined With Chemotherapy Versus Imatinib Combined With Chemotherapy in Patients With Newly Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ALL)

Conditions
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Ph+ ALL

Intervention / Treatment
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* Drug: Olverembatinib
* Drug: Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the WHO 2016 Ph chromosome or BCR/ABL1 positive Ph+ALL diagnostic and typing criteria for acute lymphoblastic leukemia. This is a newly diagnosed Ph+ALL. Expected survival of at least 3 months. ECOG ≤ 2. Adequate organ function. Use effective contraception during treatment and for at least three months after the last dose of the study drug, and male patients may not donate sperm. Pregnancy test results of serum samples obtained within 7 days prior to the first dosing of a fertile female subject were negative. Understand and voluntarily sign the informed consent approved by the Ethics Committee (EC) and voluntarily complete the study procedure and follow-up examination. Exclusion Criteria: A history of chronic myeloid leukemia and a diagnosis of acute leukemia with chronic myeloid leukemia. Clinical manifestations of central nervous system (CNS) leukemia or ALL extramedullary infiltration, except lymphadenopathy or hepatosplenomegaly. Previous or current clinical CNS diseases. Autoimmune diseases that may involve the CNS. Use therapeutic doses of anticoagulants and/or antiplatelet agents but allow low doses of anticoagulants to keep central venous lines open. Use a therapeutic drug that has drug interaction with the investigational drug due to other diseases within 7 days prior to the first receipt of the investigational drug. Uncontrolled Heart diseases. Had any VTE in the 6 months prior to randomization, including but not limited to deep vein thrombosis (DVT) or pulmonary embolism. Use of prohibited drugs. The presence of any disease or medical condition that is unstable or may affect its safety or compliance with the study. Medications known to cause prolonged QT interval. Active infections requiring systemic treatment. Disease that severely affects the oral administration and absorption of drugs, or an active gastrointestinal ulcer. Contraindications to the use of glucocorticoids, and the researchers judge that they are not suitable to participate in this study. Bleeding disorders unrelated to the tumor. Plan to undergone major surgery. Allergy to drug ingredients, excipients, or their analogues in the study. Female subjects who are pregnant or breastfeeding or expect to become pregnant during the study plan or within 3 months of the last dosing. Other malignant tumors within 2 years. Any symptom or illness that may interfere with the evaluation of the efficacy and safety of the investigational drug, or any other condition or condition that is not appropriate for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olverembatinib<br>Olverembatinib in combination with chemotherapy | Drug: Olverembatinib<br>* Orally, once every other day (QOD).<br>|
| Active Comparator: Imatinib<br>Imatinib in combination with chemotherapy | Drug: Imatinib<br>* Orally, once daily (QD).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal residual disease negativity rate | The minimal residual disease negativity rate of olverembatinib combined chemotherapy versus imatinib combined chemotherapy in subjects with newly diagnosed Ph+ALL. | Cycles 1 to cycle 3 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. | According to CTCAE v5.0, the number and frequency of adverse events of test drug were assessed. | Through study completion,an average of 2 years. | 
| Plasma concentrations of olverembatinib | Blood samples will be collected to measure the plasma concentration of olverembatinib. | Cycle 1 to Cycle 3 (each cycle is 28 days) | 
| The patients' score of EORTC(The European Organization for Research and Treatment of Cancer) QLQ-C30. | To evaluate patient-reported outcome in patients treated with olverembatinib plus chemotherapy.（The scale ranges from 0 to 100, with a lower score indicating better quality of life and a higher score on the scale indicating worse symptoms.） | Through study completion,an average of 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ph+ ALL, Olverembatinib Tablets