This phase II trial tests how well etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) with or without rituximab plus recombinant Erwinia asparaginase (JZP458) works in treating patients with newly diagnosed Philadelphia chromosome (Ph) negative B-acute lymphoblastic leukemia (ALL) or T-ALL. Chemotherapy drugs, such as etoposide, vincristine, cyclophosphamide and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as prednisone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. JZP458 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving DA-EPOCH with or without rituximab plus JZP458 may kill more cancer cells in patients with newly diagnosed Ph negative B-ALL or T-ALL.
Adults (age 18 years and older) with newly-diagnosed Ph- B-ALL or T-ALL
In the opinion of the treating investigator, patients must be an unsuitable candidate for a pediatric-inspired regimen, reasons for which may include (but not be limited to) older age (e.g., ≥ 40 years), practical/logistical barriers to or toxicity concerns from administration of a pediatric-inspired regimen
Marrow or blood involvement by ALL detectable by multi-parameter flow cytometry (MFC)
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. (Performance status of 3 will be allowed if poor performance status is thought to be directly secondary to ALL.)
Prior systemic therapy for ALL except to control acute symptoms and/or leukocytosis (e.g., corticosteroids, cytarabine, etc.). Cytarabine 500 mg/m² per dose up to 2 doses and/or the equivalent of prednisone 50 mg/m²/day for up to 2 days are permitted
Burkitt lymphoma/leukemia
Isolated extramedullary or known parenchymal central nervous system (CNS) disease
Known hypersensitivity or intolerance to any of the agents under investigation
Single group
Asparaginase Erwinia chrysanthemi
DrugGiven IM
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Collection
Procedure/SurgeryUndergo bone marrow sample collection
Computed Tomography
Procedure/SurgeryUndergo CT or PET/CT
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven CIV
Etoposide
DrugGiven CIV
Filgrastim
Biological/VaccineGiven SC
Pegfilgrastim
Biological/VaccineGiven SC
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Vincristine
DrugGiven CIV
Measurable residual disease (MRD) negativity
Will be measured by multi-parameter flow cytometry (MFC). Will be assessed according to the National Comprehensive Cancer Network response criteria.
MRD negativity
Will be measured by MFC. Will be assessed descriptively, using means, medians, and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures.
Incidence of grade 3 or higher non-hematologic adverse events (AEs)
Will be assessed descriptively, using means, medians, and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures. The incidence of AEs will be reported as ratios or percentages.
Event-free survival (EFS)
Will be assessed descriptively, using means, medians, and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures. Kaplan-Meier curves will be used to depict EFS.
Relapse-free survival (RFS)
Will be assessed descriptively, using means, medians, and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures. Kaplan-Meier curves will be used to depict RFS.
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University of Washington
Lead sponsor
Jazz Pharmaceuticals
Collaborator
