Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) ± Rituximab + Recombinant Erwinia Asparaginase (JZP458; Rylaze®) for the Treatment of Newly-Diagnosed Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Lymphoma/Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; T Acute Lymphoblastic Leukemia
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Cyclophosphamide; Drug: Prednisone; Biological: Pegfilgrastim; Biological: Filgrastim; Biological: Rituximab; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Drug: Asparaginase Erwinia chrysanthemi; Procedure: Bone Marrow Collection; Drug: Doxorubicin; Drug: Etoposide; Drug: Vincristine

Detailed 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, 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
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kim Quach; Phone Number: 206-606-8311; Email: kquach@fredhutch.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Kim Quach; Phone Number: 206-606-8311; Email: kquach@fredhutch.org
      • Principal Investigator: Ryan D. Cassaday, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (age 18 years and older) with newly-diagnosed Ph- B-ALL or T-ALL
• In the opinion of the treating investigator, patients must be an unsuitable candidate for a pediatric-inspired regimen, reasons for which may include (but not be limited to) older age (e.g., ≥ 40 years), practical/logistical barriers to or toxicity concerns from administration of a pediatric-inspired regimen
• Marrow or blood involvement by ALL detectable by multi-parameter flow cytometry (MFC)
• 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.)
• Total bilirubin ≤ 2.0 x upper limit of normal (ULN) (unless attributed to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be ≤ 4.0 x ULN) (Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is ≤ 5.0 x ULN and alanine aminotransferase [ALT]/aspartate aminotransferase [AST] are ≤ 8.0 x ULN.)
• AST (serum glutamic oxaloacetic transaminase [SGOT])/ALT (serum glutamic pyruvic transaminase [SGPT]) ≤ 5.0 x institutional ULN. (Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is ≤ 5.0 x ULN and ALT/AST are ≤ 8.0 x ULN.)
• Calculated creatinine clearance of ≥ 60 ml/min/1.73 m^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
• Ability to give informed consent and comply with the protocol
• Anticipated survival of at least 3 months, independent of ALL
• Female subjects of childbearing potential should use effective non-hormonal contraceptive methods during treatment with JZP458 and for 3 months after the last dose of study drug. Male subjects with female partners of childbearing potential must agree to use an effective method of birth control from the time of signing the consent form until at least 3 months after the last dose of study drug

Exclusion Criteria:

• Prior systemic therapy for ALL except to control acute symptoms and/or leukocytosis (e.g., corticosteroids, cytarabine, etc.). Cytarabine 500 mg/m^2 per dose up to 2 doses and/or the equivalent of prednisone 50 mg/m^2/day for up to 2 days are permitted
• Burkitt lymphoma/leukemia
• Isolated extramedullary or known parenchymal central nervous system (CNS) disease
• Known hypersensitivity or intolerance to any of the agents under investigation
• Known history of grade 3+ pancreatitis or chronic pancreatic insufficiency
• Known active chronic liver disease including, but not limited to, non-alcoholic steatohepatitis, cirrhosis, or non-alcoholic fatty liver disease
• Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol

• Pregnant or nursing

  • Pregnancy test is only required in women, unless they are highly unlikely to conceive (defined as [1] surgically sterilized, or [2] postmenopausal [i.e., a woman who is > 50 years old or who has not had menses for ≥ 1 year], or [3] not heterosexually active)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (DA-EPOCH, rituximab, JZP458); Patients receive etoposide IV, doxorubicin IV and vincristine IV over 96 hours on days 1-4, cyclophosphamide IV over 1 hour on day 5, prednisone PO 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 IM 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 SC once or filgrastim SC QD until 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 CT or PET/CT throughout the study.

Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; B 518; B518; WR 138719; WR138719; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; filgrastim-SD/01; Fulphila; HSP-130; Jinyouli; Neulasta; Neulastim; 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-jmdb; PF-06881894; SD-01; SD-01 sustained duration G-CSF; Udenyca; Ziextenzo; Neupopeg; Pegylated G-CSF; Pegylated GCSF; Pegylated Granulocyte Colony Stimulating Factor; Pegfilgrastim-apgf; Pegfilgrastim-bmez; Pegfilgrastim-cbqv; Dulastin; Tripegfilgrastim; Fylnetra; G-Lasta; Pegfilgrastim-fpgk; Pegfilgrastim-pbbk; Stimufend; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Filgrastim-aafi; Nivestym; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Filgrastim Biosimilar Filgrastim-sndz; Zarxio; Filgrastim XM02; Tbo-filgrastim; Granix; Nivestim; XM02; Filgrastim-sndz; Filgrastim Biosimilar Tbo-filgrastim; Filgrastim-ayow; Releuko; Neutroval; Biological: Rituximab; Given IV; Other Names: Rituxan; MabThera; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Monoclonal Antibody IDEC-C2B8; PF-05280586; Riabni; Rituximab ABBS; Rituximab ARRX; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; 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-arrx; Rituximab-pvvr; RTXM83; Ruxience; Truxima; Rixathon; Ikgdar; Mabtas; Rituximab-abbs; BI-695500; BI695500; Blitzima; IDEC 102; IDEC102; PF 05280586; PF05280586; Ritemvia; Rituximab-blit; Rituximab-rite; Rituximab-rixa; Rituximab-rixi; Riximyo; RTXM 83; RTXM-83; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Drug: Asparaginase Erwinia chrysanthemi; Given IM; Other Names: JZP458; Crisantaspase; Crisantaspasum; Erwinase; Erwinaze; Asparaginase Erwinia chrysanthemi-rywn; Crisantaspase Biobetter JZP-458; JZP 458; JZP-458; PF743; RC-P JZP-458; Recombinant Asparaginase erwinia chrysanthemi JZP-458; Recombinant Crisantaspase JZP-458; Recombinant Erwinia asparaginase JZP-458; Rylaze; Asparaginase Erwinia chrysanthemi (Recombinant)-rywn; Asparaginase Erwinia chrysanthemi, Recombinant-rywn; Enrylaze; Procedure: Bone Marrow Collection; Undergo bone marrow sample collection; Other Names: Collection, Bone Marrow; Drug: Doxorubicin; Given CIV; Other Names: Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Etoposide; Given CIV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; VP 16213; VP-16213; VP16213; Drug: Vincristine; Given CIV; Other Names: VCR; Leurocristine; Vincrystine; LCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurable 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.	After 4 cycles of treatment (cycle length = 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Ryan D. Cassaday, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Burkitt Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hydrocarbons; Hydrocarbons, Cyclic; Biological Factors; Carbohydrates; Alkaloids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Hydrolases; Enzymes; Enzymes and Coenzymes; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Chemistry Techniques, Analytical; Spectrum Analysis; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Intercellular Signaling Peptides and Proteins; Pregnadienediols; Amidohydrolases; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Glycoproteins; Glycoconjugates; Antibodies, Monoclonal, Murine-Derived; Daunorubicin; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Rituximab; Prednisone; Cyclophosphamide; Etoposide; Doxorubicin; Vincristine; Asparaginase; Specimen Handling; Magnetic Resonance Spectroscopy; CT-P10; Granulocyte Colony-Stimulating Factor; Filgrastim; deltacortene; prednylidene; pegfilgrastim; asparaginase erwinia chrysanthemi recombinant; pegylated granulocyte colony-stimulating factor
• Other Study ID Numbers: RG1124788; NCI-2024-09417 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); FHIRB0020869 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No