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

NCT ID: NCT06738368

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2028-07-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative T Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Asparaginase Erwinia chrysanthemi

Intervention Type DRUG

Given IM

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Marrow Collection

Intervention Type PROCEDURE

Undergo bone marrow sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT or PET/CT

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given CIV

Etoposide

Intervention Type DRUG

Given CIV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Pegfilgrastim

Intervention Type BIOLOGICAL

Given SC

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Prednisone

Intervention Type DRUG

Given PO

Rituximab

Intervention Type BIOLOGICAL

Given IV

Vincristine

Intervention Type DRUG

Given CIV

Interventions

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Asparaginase Erwinia chrysanthemi

Given IM

Intervention Type DRUG

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Marrow Collection

Undergo bone marrow sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT or PET/CT

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Doxorubicin

Given CIV

Intervention Type DRUG

Etoposide

Given CIV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Pegfilgrastim

Given SC

Intervention Type BIOLOGICAL

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Prednisone

Given PO

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Vincristine

Given CIV

Intervention Type DRUG

Other Intervention Names

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Asparaginase Erwinia chrysanthemi (Recombinant)-rywn Asparaginase Erwinia chrysanthemi, Recombinant-rywn Asparaginase Erwinia chrysanthemi-rywn Crisantaspase Crisantaspase Biobetter JZP-458 Crisantaspasum Enrylaze Erwinase Erwinaze JZP 458 JZP-458 JZP458 PF743 RC-P JZP-458 Recombinant Asparaginase erwinia chrysanthemi JZP-458 Recombinant Crisantaspase JZP-458 Recombinant Erwinia asparaginase JZP-458 Rylaze Biological Sample Collection Biospecimen Collected Specimen Collection Collection, Bone Marrow CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography (-)-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 Adriablastin Hydroxydaunomycin Hydroxyl Daunorubicin Hydroxyldaunorubicin Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP 16213 VP-16 VP-16-213 VP-16213 VP16 VP16213 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 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 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT .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 ABP 798 BI 695500 BI-695500 BI695500 Blitzima C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 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 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 LCR Leurocristine VCR Vincrystine

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ryan D. Cassaday, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Central Contacts

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Kim Quach

Role: CONTACT

Phone: 206-606-8311

Email: [email protected]

Facility Contacts

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Kim Quach

Role: primary

Other Identifiers

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NCI-2024-09417

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020869

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124788

Identifier Type: -

Identifier Source: org_study_id