NCT07224100 · University of Washington
Dose-Adjusted EPOCH With or Without Rituximab Plus Ponatinib for the Treatment of Newly-Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia/Lymphoma
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the TBili is ≤ 5 x ULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 x institutional ULN
- (Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the ALT/AST are ≤ 8 x ULN)
- Calculated creatinine clearance of \> 30 ml/min/1.73m\^2, as measured by the Modification of Diet in Renal Disease (MDRD) equation, will be eligible
- As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment. However, adequate recovery of blood counts will be required to receive subsequent cycles
- 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)
- Ability to give informed consent and comply with the protocol
- Anticipated survival of at least 3 months, independent of ALL
- Female subjects of reproductive potential must agree to use an effective method of birth control from the time of signing the consent form until one of the following:
- For subjects not expected to receive rituximab (i.e., CD20-negative): at least 3 weeks after the last dose of ponatinib, or
- For subjects expected to receive rituximab (i.e., CD20-positive): at least 12 months after the last dose of rituximab
- A subject does not have reproductive potential if they are (1) surgically sterilized, or (2) postmenopausal (i.e., a female who is \> 50 years old or who has not had menses for ≥ 1 year), or (3) not heterosexually active
- Male subjects must agree to use an effective method of birth control and to not donate sperm from the time of signing the consent form until at least 3 weeks after the last dose of ponatinib
Exclusion criteria
- 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
- Symptomatic atherosclerotic cardiovascular disease (e.g., myocardial infarction, cerebrovascular accident, peripheral arterial disease, etc.) within 1 year of enrollment
- Active resistant hypertension, defined as having an ambulatory blood pressure above goal despite use of 3 antihypertensive medications from different classes
- Venous thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months of enrollment
- Known hypersensitivity or intolerance to any of the agents under investigation
- Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol
- May not be pregnant or nursing. Pregnancy test is only required in females, unless they do not have reproductive potential. For subjects not expected to receive rituximab (i.e., CD20-negative), nursing can occur 1 week after the last dose of ponatinib. For subjects expected to receive rituximab (i.e., CD20-positive), nursing can occur 6 months after the last dose of rituximab
Where
- Seattle, Washington
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 16, 2026 · Source of record for eligibility and locations