Dose-Adjusted EPOCH With or Without Rituximab Plus Ponatinib for the Treatment of Newly-Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia/Lymphoma

NCT07224100 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1125799NCI-2025-07631FHIRB0021018
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphoblastic Lymphoma; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Lymphoblastic Leukemia/Lymphoma With t(9;22)(q34.1;q11.2); BCR-ABL1

Outcome Measures

Primary Outcomes (1)

• Rate of complete molecular response

  Will be evaluated by BCR::ABL1 reverse transcriptase polymerase chain reaction.

  Up to completion of 4 cycles (approximately 3 months) (cycle length = 21 days)

Secondary Outcomes (7)

• Incidence of non-hematologic toxicities greater than or equal to grade 3

  Up to 30 days after last dose of study treatment

• Incidence of serious adverse events

  Up to 30 days after last dose of study treatment

• Frequency of patients unable to complete one full cycle of etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin +/- rituximab + ponatinib (Feasibility)

  Up to 5 years after last dose of study treatment

• Event-free survival

  Up to 5 years after last dose of study treatment

• Relapse-free survival

  Up to 5 years after last dose of study treatment

Study Arms (1)

Treatment (DA-EPOCH, rituximab, ponatinib)

EXPERIMENTAL

Patients receive etoposide IV, doxorubicin IV, and vincristine IV over 96 hours on days 1-4, cyclophosphamide IV over 1 hour on day 5, and prednisone PO BID on days 1-5 and ponatinib PO QD on days 1-21 of each cycle. Patients receive filgrastim SC on day 6, 7, or 8 and continue until 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 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, bone marrow aspiration and biopsy and CT throughout the study. Additionally, patients may undergo PET/CT at enrollment.

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Etoposide; Biological: Filgrastim; Biological: Pegfilgrastim; Drug: Ponatinib; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (DA-EPOCH, rituximab, ponatinib)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (DA-EPOCH, rituximab, ponatinib)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

Treatment (DA-EPOCH, rituximab, ponatinib)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio

Treatment (DA-EPOCH, rituximab, ponatinib)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Dulastin, Filgrastim SD-01, filgrastim-SD/01, Fulphila, Fylnetra, G-Lasta, HSP-130, Jinyouli, Neulasta, Neulastim, Neupopeg, Nyvepria, PEG-filgrastim, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar PF-06881894, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, Pegfilgrastim-apgf, Pegfilgrastim-bmez, Pegfilgrastim-cbqv, Pegfilgrastim-fpgk, Pegfilgrastim-jmdb, Pegfilgrastim-pbbk, Pegylated G-CSF, Pegylated GCSF, Pegylated Granulocyte Colony Stimulating Factor, PF-06881894, SD-01, SD-01 sustained duration G-CSF, Stimufend, Tripegfilgrastim, Udenyca, Ziextenzo

Treatment (DA-EPOCH, rituximab, ponatinib)

Ponatinib DRUG

Given PO

Also known as: AP 24534, AP-24534, AP24534

Treatment (DA-EPOCH, rituximab, ponatinib)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (DA-EPOCH, rituximab, ponatinib)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Treatment (DA-EPOCH, rituximab, ponatinib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (DA-EPOCH, rituximab, ponatinib)

Vincristine DRUG

Given IV

Also known as: LCR, Leurocristine, VCR, Vincrystine

Treatment (DA-EPOCH, rituximab, ponatinib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (DA-EPOCH, rituximab, ponatinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (DA-EPOCH, rituximab, ponatinib)

Computed Tomography PROCEDURE

Undergo CT and PET/CT

Also known as: CAT, CAT scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography (CT) scan, CT, CT scan, Diagnostic CAT Scan

Treatment (DA-EPOCH, rituximab, ponatinib)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET scan, Positron Emission Tomography Scan, PT

Treatment (DA-EPOCH, rituximab, ponatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Takeda: collaborator
• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Doxorubicin; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; pegfilgrastim; pegylated granulocyte colony-stimulating factor; ponatinib; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Ryan Cassaday, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan Cassaday, MD

CONTACT

206-606-6744; cassaday@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2025
• First Posted: November 4, 2025
• Study Start: March 30, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)