Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Study Details
Study Description
Brief Summary
The pediatric-inspired regimen has greatly improved the prognosis of adult patients with with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), but relapse remains a great challenge. Venetoclax (Ven) is an oral, selective inhibitor of B-cell lymphoma 2 (Bcl-2). Although this drug is currently used primarily for acute myeloid leukemia, in vitro as well as small cohort studies suggest a effect in acute lymphoblastic leukemia. This study proposes to combine pediatric-inspired regimen with venetoclax for the treatment of adult patients with Ph- ALL, aiming to improve the MRD-negative complete remission rate measured by flow cytometry after induction and to reduce relapse, thus further improving patients overall survival.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Pediatric-inspired Regimen Combined With Venetoclax
|
Drug: Vincristine
Anti-tumor alkaloids
Drug: Daunorubicin
Anthracycline
Drug: Cyclophosphamide
Alkylating agent
Drug: Pegaspargase
Polyethylene glycol (PEG) conjugated to L-asparaginase
Drug: Prednisone
Glucocorticoids
Drug: Cytarabine
Pyrimidine antimetabolites
Drug: 6-mercaptopurine
Cell cycle-specific antitumor drug
Drug: Dexamethasone
Glucocorticoids
Drug: Methotrexate
Antifolate antineoplastic drug
Drug: Venetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
|
Outcome Measures
Primary Outcome Measures
- MRD-negative complete remission rate measured by flow cytometry [After induction (4 week)]
Secondary Outcome Measures
- Complete remission (CR) rate [After 2 cycles of chemotherapy, an expected average of 3 months]
- Overall survival (OS) [Up to 5 years post-registration]
From the date of registration to the date of death resulting from any cause
- Relapse free survival (RFS) [Up to 5 years post-registration]
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
- Disease-free Survival (DFS) [Up to 5 years post-registration]
From CR1 to relapse, death from any cause or last follow-up
- The rate of adverse events [An expected average of 24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification
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Age: 14 -60 years
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Male or female
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ECOG Performance Status 0-2
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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%;
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Subject has provided written informed consent prior to any screening procedure
Exclusion Criteria:
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Burkitt lymphoma/leukemia
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Acute Leukemia of Ambiguous Lineage
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Female patients who are pregnant or breast feeding
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Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
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History of pancreatitis
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Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of
7.5%. Patients with preexisting, well-controlled diabetes are not excluded
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History of active gastrointestinal bleeding within the last 6 months
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History of arterial/venous thrombosis within the last 6 months
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Known HIV seropositivity
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Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Institute of Hematology & Blood Diseases Hospital | Tianjin | China | 300020 |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
Investigators
- Principal Investigator: Jianxiang Wang, Dr, Institute of Hematology & Blood Diseases Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IIT2022052-EC-1