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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given IM
Undergo blood sample collection
Undergo bone marrow sample collection
Undergo CT or PET/CT
Given IV
Given CIV
Given CIV
Given SC
Given SC
Undergo PET/CT
Given PO
Given IV
Given CIV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGMeasurable 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)
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.
Time frame: After 1 cycle of study therapy (cycle length = 21 days)
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.
Time frame: Up to 30 days after last dose of study treatment
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.
Time frame: Up to 5 years
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.
Time frame: Up to 5 years
Overall survival (OS)
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 OS.
Time frame: Up to 5 years
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