Clinical trial NCT06051409: A Study of Olverembatinib in Patients With Newly Diagnosed Ph+ALL.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ph+ ALL
Keywords: Ph+ ALL
Olverembatinib Tablets
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
Collaborators: name: HealthQuest Pharma Inc.
First posted: 2023-09-22
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: Comparing efficacy and safety of Olverembatinib in combination with chemotherapy (investigational arm) vs. Imatinib in combination with chemotherapy (control arm).

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Expected survival of at least 3 months.
3. ECOG ≤ 2.
4. Adequate organ function.
5. 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.
6. Pregnancy test results of serum samples obtained within 7 days prior to the first dosing of a fertile female subject were negative.
7. 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:

1. A history of chronic myeloid leukemia and a diagnosis of acute leukemia with chronic myeloid leukemia.
2. Clinical manifestations of central nervous system (CNS) leukemia or ALL extramedullary infiltration, except lymphadenopathy or hepatosplenomegaly.
3. Previous or current clinical CNS diseases.
4. Autoimmune diseases that may involve the CNS.
5. Use therapeutic doses of anticoagulants and/or antiplatelet agents but allow low doses of anticoagulants to keep central venous lines open.
6. 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.
7. Uncontrolled Heart diseases.
8. Had any VTE in the 6 months prior to randomization, including but not limited to deep vein thrombosis (DVT) or pulmonary embolism.
9. Use of prohibited drugs.
10. The presence of any disease or medical condition that is unstable or may affect its safety or compliance with the study.
11. Medications known to cause prolonged QT interval.
12. Active infections requiring systemic treatment.
13. Disease that severely affects the oral administration and absorption of drugs, or an active gastrointestinal ulcer.
14. Contraindications to the use of glucocorticoids, and the researchers judge that they are not suitable to participate in this study.
15. Bleeding disorders unrelated to the tumor.
16. Plan to undergone major surgery.
17. Allergy to drug ingredients, excipients, or their analogues in the study.
18. Female subjects who are pregnant or breastfeeding or expect to become pregnant during the study plan or within 3 months of the last dosing.
19. Other malignant tumors within 2 years.
20. 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.

Primary outcomes:
measure: Minimal residual disease negativity rate
timeFrame: Cycles 1 to cycle 3 (each cycle is 28 days)
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
timeFrame: Through study completion,an average of 2 years.
measure: Plasma concentrations of olverembatinib
timeFrame: Cycle 1 to Cycle 3 (each cycle is 28 days)
measure: The patients' score of EORTC(The European Organization for Research and Treatment of Cancer) QLQ-C30.
timeFrame: Through study completion,an average of 2 years.
Other outcomes:
Locations:
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Washington
city: Bengbu
country: China
facility: The First Affiliated Hospitalo of Bengbu Medical School
state: Anhui
city: Chongqing
country: China
facility: Xinqiao Hospital of Army Medical University
state: Chongqing
city: Guangdong
country: China
facility: Guangdong Province People's Hospital
state: Guangzhou
city: Guangdong
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangzhou
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital of Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Suzhou
country: China
facility: The first affiliated hospital of Suzhou University
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine Ruijin Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of blood transfusion of Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Shanghai Jiaotong University School of Medicine Ruijin Hospital
name: Weili Zhao, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Suzhou Medical College
name: Suning Chen, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: