This phase II trial tests the effect of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) with or without rituximab plus ponatinib in treating patients newly diagnosed with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia or lymphoma (ALL). Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill cancer cells. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is a drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. Doxorubicin comes from the bacterium Streptomyces peucetius. It damages DNA and may kill cancer cells. It is a type of anthracycline antitumor antibiotic. DA-EPOCH involves a longer exposure time to doxorubicin, vincristine and etoposide compared to a higher concentration over a shorter time which may provide better tumor response. 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. Ponatinib blocks BCR::ABL1 and other proteins, which may help keep cancer cells from growing and may kill them. It may also prevent the growth of new blood vessels that tumors need to grow. Ponatinib is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Giving DA-EPOCH with or without rituximab plus ponatinib may be safe, tolerable, and/or effective in treating patients with newly diagnosed Ph+ ALL.
Adults (age 18 years and older) with newly-diagnosed Ph+ B-ALL. Ph status will be determined by routine cytogenetics, fluorescence in situ hybridization (FISH), and/or reverse transcriptase-polymerase chain reaction (RT-PCR) for the BCR::ABL1 translocation
Marrow or blood involvement by abnormal lymphoblasts detectable by multiparameter flow cytometry (MFC)
Total bilirubin (TBili) ≤ 1.5 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point TBili must be ≤ 4 x ULN)
(Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the TBili is ≤ 5 x ULN)
Burkitt lymphoma/leukemia
No prior systemic therapy for ALL except to control acute symptoms and/or hyperleukocytosis (e.g., corticosteroids, cytarabine, etc.)
No isolated extramedullary or known parenchymal central nervous system (CNS) disease
History of acute pancreatitis within 1 year of enrollment or known chronic pancreatitis
Single group
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven IV
Etoposide
DrugGiven IV
Filgrastim
Biological/VaccineGiven SC
Pegfilgrastim
Biological/VaccineGiven SC
Ponatinib
DrugGiven PO
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Vincristine
DrugGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Computed Tomography
Procedure/SurgeryUndergo CT and PET/CT
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Rate of complete molecular response
Will be evaluated by BCR::ABL1 reverse transcriptase polymerase chain reaction.
Incidence of non-hematologic toxicities greater than or equal to grade 3
Will be graded in severity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0. Will be reported as ratios/percentages. Will exclude asymptomatic grade 3 laboratory abnormalities.
Incidence of serious adverse events
Will be graded in severity using NCI CTCAE v 6.0. Will be reported as ratios/percentages.
Frequency of patients unable to complete one full cycle of etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin +/- rituximab + ponatinib (Feasibility)
Will be assessed descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present).
Event-free survival
Will be assessed descriptively, using means and associated confidence intervals for continuous measures, simple ratios and Clopper-Pearson confidence intervals for binary measures, and either Kaplan-Meier or cumulative incidence estimates for time-to-event outcomes (depending on whether competing risks are present). Kaplan-Meier curves will be used to depict survival.
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University of Washington
Lead sponsor
Takeda
Collaborator
