DA-EPOCH chemotherapy with optional rituximab plus JZP458 (Erwinia asparaginase) for adults with newly diagnosed Ph‑negative B‑ALL or T‑ALL
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 trial tests whether adding JZP458 (a recombinant Erwinia asparaginase) to DA‑EPOCH chemotherapy, with or without rituximab, helps adults newly diagnosed with Philadelphia chromosome–negative B‑ or T‑cell acute lymphoblastic leukemia.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Washington Academic / other |
| Drugs / interventions | prednisone, rituximab, Chemotherapy, cyclophosphamide, doxorubicin |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT06738368 on ClinicalTrials.gov |
What this trial studies
Adults receive cycles of DA‑EPOCH chemotherapy (etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone) every 21 days for up to eight cycles, with rituximab given to CD20‑positive patients. JZP458 is given by intramuscular injection on days 7–21 of each cycle for up to seven doses, and growth factor support (pegfilgrastim or filgrastim) is used after day 6–8 to manage neutropenia. Patients undergo periodic blood and bone marrow sampling and imaging for extramedullary disease as needed, and are followed every 3 months for 2 years then every 6 months up to 3 additional years. Treatment continues until disease progression or unacceptable toxicity.
Who should consider this trial
Good fit: Adults 18 years and older with newly diagnosed Philadelphia chromosome–negative B‑ALL or T‑ALL who are considered unsuitable for pediatric‑inspired regimens, with measurable marrow or blood disease and ECOG performance status up to 2 (or 3 if due to leukemia).
Not a fit: Patients with Philadelphia chromosome–positive ALL, prior definitive therapy for ALL, or those who can receive and tolerate pediatric‑inspired regimens are less likely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this regimen could improve remission rates and provide an alternative asparaginase option for adults who cannot receive pediatric‑style regimens.
How similar studies have performed: Asparaginase‑containing regimens have a history of benefit in ALL and Erwinia‑derived asparaginase formulations have been used before, but combining JZP458 with DA‑EPOCH in this adult population is a relatively new approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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)
Where this trial is running
Seattle, Washington
- Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Ryan D. Cassaday, MD — Fred Hutch/University of Washington Cancer Consortium
- Study coordinator: Kim Quach
- Email: kquach@fredhutch.org
- Phone: 206-606-8311
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.