Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions
Keywords
Philadelphia Chromosome-Negative, Acute Lymphoblastic Leukemia, Adolescent and Adult, Pediatric-inspired Regimen, Venetoclax
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.
Interventions
DRUGPegaspargase
Polyethylene glycol (PEG) conjugated to L-asparaginase
DRUGVincristine
Anti-tumor alkaloids
DRUGDaunorubicin
Anthracycline
DRUGCyclophosphamide
Alkylating agent
DRUGPrednisone
Glucocorticoids
DRUGCytarabine
Pyrimidine antimetabolites
DRUG6-mercaptopurine
Cell cycle-specific antitumor drug
DRUGDexamethasone
Glucocorticoids
DRUGMethotrexate
Antifolate antineoplastic drug
DRUGVenetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
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 60 Years
Healthy volunteers
No
Inclusion criteria
* 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 * Age: 14 -60 years * Male or female * ECOG Performance Status 0-2 * 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%; * Subject has provided written informed consent prior to any screening procedure
Exclusion criteria
* Burkitt lymphoma/leukemia * Acute Leukemia of Ambiguous Lineage * Female patients who are pregnant or breast feeding * Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment * History of pancreatitis * Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of \>7.5%. Patients with preexisting, well-controlled diabetes are not excluded * History of active gastrointestinal bleeding within the last 6 months * History of arterial/venous thrombosis within the last 6 months * Known HIV seropositivity * Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MRD-negative complete remission rate measured by flow cytometry | After induction (4 week) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
China
Contacts
Primary ContactJianxiang Wang, Dr
Outcome results
None listed