Phase II Study of Dose-Adjusted EPOCH ± Rituximab + Ponatinib for Adults With Newly-Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia/Lymphoma
University of Washington
Summary
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.
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, and prednisone orally (PO) twice daily (BID) on days 1-5 and ponatinib PO once daily (QD) on days 1-21 of each cycle. Patients receive filgrastim subcutaneously (SC) on day 6, 7, or 8 and continue until absolute neutrophil count (ANC) \> 2000/µL past nadir or pegfilgrastim SC on day 6, 7, or 8 of each cycle. Patients who are CD20 positive also receive rituximab IV on day 1 or 5 of each cycle. Cycles repeat every 21 days for up to 8 cyc…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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: Pat…
Interventions
- DrugCyclophosphamide
Given IV
- DrugDoxorubicin
Given IV
- DrugEtoposide
Given IV
- BiologicalFilgrastim
Given SC
- BiologicalPegfilgrastim
Given SC
- DrugPonatinib
Given PO
- DrugPrednisone
Given PO
- Biological
Location
- Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington