Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) ± Rituximab + Recombinant Erwinia Asparaginase (JZP458; Rylaze®) for the Treatment of Newly-Diagnosed Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Lymphoma/Leukemia
Summary
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.
Detailed description
OUTLINE: Patients receive etoposide intravenously (IV), doxorubicin IV and vincristine IV over 96 hours on days 1-4, cyclophosphamide IV over 1 hour on day 5, prednisone orally (PO) twice daily (BID) on days 1-5 of each cycle. In addition, CD20 positive patients receive rituximab IV on day 1 or 5 of each cycle. Patients also receive JZP458 intramuscularly (IM) once every 2-3 days on days 7-21 for up to 7 doses. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 6, 7, or 8, patients also receive pegfilgrastim subcutaneously (SC) once or filgrastim SC once daily (QD) until absolute neutrophil count (ANC) \> 2000/uL past nadir. Patients also undergo blood sample collection and bone marrow collection throughout the study. Additionally, patients with extramedullary disease may undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for up to 3 years.
Arms & interventions
- DrugAsparaginase Erwinia chrysanthemi
Given IM
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Collection
Undergo bone marrow sample collection
- ProcedureComputed Tomography
Undergo CT or PET/CT
- DrugCyclophosphamide
Given IV
- DrugDoxorubicin
Given CIV
- DrugEtoposide
Given CIV
- BiologicalFilgrastim
Given SC
- BiologicalPegfilgrastim
Given SC
- ProcedurePositron Emission Tomography
Undergo PET/CT
- DrugPrednisone
Given PO
- BiologicalRituximab
Given IV
- DrugVincristine
Given CIV
Outcome measures
Primary
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.
Time frame: After 4 cycles of treatment (cycle length = 21 days)
Secondary
MRD negativity
Time frame: After 1 cycle of study therapy (cycle length = 21 days)
Incidence of grade 3 or higher non-hematologic adverse events (AEs)
Time frame: Up to 30 days after last dose of study treatment
Event-free survival (EFS)
Time frame: Up to 5 years
Relapse-free survival (RFS)
Time frame: Up to 5 years
Overall survival (OS)
Time frame: Up to 5 years
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109