Erwinia asparaginase with chemotherapy for high‑risk adults with newly diagnosed Philadelphia‑negative acute lymphoblastic leukemia or lymphoblastic lymphoma
A Phase 2 Study Evaluating the Safety and Efficacy of Asparaginase Erwinia Chrysanthemi- Recombinant-Rywn (Recombinant Erwinia Asparaginase) During Pediatric-Inspired Regimen in High-Risk Adults With Newly Diagnosed ALL or LBL
This trial tries Erwinia-derived asparaginase together with induction and consolidation chemotherapy in adults 18–54 with newly diagnosed high‑risk, Philadelphia chromosome–negative ALL or lymphoblastic lymphoma.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 53 (estimated) |
| Ages | 18 Years to 54 Years |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | rituximab, chemotherapy, methotrexate, cyclophosphamide |
| Locations | 8 sites (Phoenix, Arizona and 7 other locations) |
| Trial ID | NCT06918431 on ClinicalTrials.gov |
What this trial studies
This is a phase II trial that gives recombinant Erwinia asparaginase (25 mg/m² every 48 hours) as the first asparaginase during induction chemotherapy with a safety lead‑in followed by an expansion cohort. Induction includes multi‑agent chemotherapy (cytarabine, dexamethasone, vincristine, daunorubicin, methotrexate, and rituximab when appropriate) and selected patients proceed to consolidation (cyclophosphamide, cytarabine, vincristine, mercaptopurine, methotrexate). Key outcomes include safety and tolerability with special attention to grade 3+ hepatotoxicity not resolving within 14 days, composite complete remission rates, and minimal residual disease negativity. The protocol also includes biospecimen collection, bone marrow assessments, and imaging to monitor response and toxicity.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18–39 with BMI ≥30 or aged 40–54 (regardless of BMI) with newly diagnosed Philadelphia‑negative ALL or lymphoblastic lymphoma who meet organ‑function and performance status (ECOG ≤2) criteria.
Not a fit: Patients with Philadelphia‑positive disease, significant liver dysfunction beyond the trial limits, age outside 18–54, or those who can tolerate standard E. coli–derived asparaginase may not receive benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could give an effective alternative asparaginase option that helps more high‑risk adults complete multi‑drug therapy and achieve remission.
How similar studies have performed: Erwinia asparaginase is an established alternative after hypersensitivity to E. coli–derived asparaginase, but using recombinant Erwinia as the first asparaginase in frontline adult induction regimens has been less well studied.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Age between 18 and 39 with body mass index (BMI) ≥ 30 or age 40-54 years, regardless of BMI * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Patients with newly diagnosed Philadelphia (Ph)-negative (-) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) according to World Health Organization (WHO) criteria * Both B- and T-cell phenotypes are allowed. * CD20+ patients only: White blood cell count less than 25 x 10\^9/L prior to initiation of rituximab (within 14 days prior to day 1 of protocol therapy) * Cytoreduction with hydroxyurea or steroid or a single dose of intrathecal chemotherapy prior to treatment may be required * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to day 1 of protocol therapy) (unless has Gilbert's disease or related to underlying leukemia, ≤ 3 x ULN) * Aspartate aminotransferase (AST) ≤ 3.0 x ULN (AST ≤ 5.0 x ULN if related to underlying leukemia) (within 14 days prior to day 1 of protocol therapy) * Note: AST ≤ 3.0 x ULN at the time of first dose of recombinant Erwinia asparaginase administration * Alanine aminotransferase (ALT) ≤ 3.0 x ULN (ALT ≤ 5.0 x ULN if related to underlying leukemia) (within 14 days prior to day 1 of protocol therapy) * Note: ALT ≤ 3.0 x ULN at the time of first dose of recombinant Erwinia asparaginase administration * Creatinine clearance of ≥ 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula (within 14 days prior to day 1 of protocol therapy) * Prothrombin (PT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy) * Activated partial thromboplastin time (aPTT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy) * Left ventricular ejection fraction (LVEF) ≥ 50% * Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy * Seronegative for active hepatitis B virus (HBV) (surface antigen negative and anti-hepatitis B virus core antibody \[HBc\] negative) for CD20+ patients only * Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential to use an effective (non-hormonal) method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy. For participants taking rituximab, effective birth control or abstinence to be used for at least 12 months after last dose * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * Leukemia-based therapy with chemotherapy with the exception of: * Cytoreduction with steroid or hydroxyurea or a single dose of intrathecal chemotherapy is allowed before initiating the study * Prior treatment with all-trans-retinoic acid (ATRA) for suspected acute promyelocytic leukemia (APL) is allowed * Received previous treatment with any other asparaginase formulation * Must not have received or planning to receive live vaccine while being on study or 2 weeks before and after completion of treatment. For CD20+ patients only: Must not have received any vaccines (live or non-live) 4 weeks before rituximab * Known presence of Philadelphia chromosome positive (Ph+; t\[9;22\]) * Class III/IV cardiovascular disability according to the New York Heart Association classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll * Parenchymal central nervous system (CNS) involvement * Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment * History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment * History of intracranial thrombosis or history of recurrent thrombosis or grade 3 and greater pulmonary embolism (except for catheter-related thrombosis) * Participants with history of grade ≥ 3 pancreatitis * History of alcohol overuse if deemed relevant in investigator opinion * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Uncontrolled active infection * Clinically significant uncontrolled illness * Other active malignancy * Females only: Pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Where this trial is running
Phoenix, Arizona and 7 other locations
- City of Hope at Phoenix — Phoenix, Arizona, United States (Recruiting)
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
- City of Hope at Irvine Lennar — Irvine, California, United States (Not_yet_recruiting)
- UC San Diego Moores Cancer Center — La Jolla, California, United States (Not_yet_recruiting)
- UCLA / Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (Not_yet_recruiting)
- University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (Not_yet_recruiting)
- Memorial Sloan Kettering Cancer Center — New York, New York, United States (Not_yet_recruiting)
- Cleveland Clinic Foundation — Cleveland, Ohio, United States (Not_yet_recruiting)
Study contacts
- Principal investigator: Ibrahim Aldoss — City of Hope Medical Center
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.