Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Conditions
Brief summary
The introduction of TKIs has greatly improved the prognosis of Ph+ ALL patients. The third-generation TKI ponatinib in combination with chemotherapy has demonstrated superior efficacy to first- and second-generation TKIs. However, unfortunately, ponatinib is not available in mainland China. Olverembatinib is the only third-generation TKI drug currently approved in mainland China. Venetoclax is an oral selective inhibitor of Bcl-2, and small exploratory clinical studies have demonstrated that venetoclax in combination with ponatinib showed high rates of CR as well as molecular response in relapsed/refractory Ph+ ALL. This study will explore the safety and efficacy of olverembatinib in combination with reduced-intensity chemotherapy and venetoclax in patients with newly diagnosed Ph+ ALL.
Interventions
DRUGOlverembatinib
a third-generation TKI
DRUGVenetoclax
a selective inhibitor of B-cell lymphoma 2 (Bcl-2)
DRUGprednisone
Glucocorticoids
DRUGVincristine
Anti-tumor alkaloids
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 14 years or older 2. Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia; Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination 3. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 4. Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%; 5. Subject has provided written informed consent prior to any screening procedure
Exclusion criteria
1. Lymphoid blast crisis of chronic myelocytic leukemia (CML) 2. Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment) 3. Clinical manifestations of CNS or extramedullary involvement with ALL 4. Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.) 5. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment 6. Known HIV seropositivity 7. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis 8. Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL) 9. Female patients who are pregnant or breast feeding 10. Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of \>7.5%. Patients with preexisting, well-controlled diabetes are not excluded 11. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CMR rate | At 3 months of treatment (90 days) | Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse free survival | up to 60 months | From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day |
| The rate of adverse events | an expected average of 24 months | — |
| Overall survival(OS) | up to 60 months | From the date of registration to the date of death resulting from any cause |
| The duration of CR | up to 60 months | — |
| The duration of molecular CR | up to 60 months | — |
| complete remission (CR) rate | an expected average of 3 months | — |
Countries
China
Outcome results
None listed