Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

NCT06918431 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24442NCI-2025-02184P30CA033572
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II trial tests the safety, side effects, and effectiveness of asparaginase Erwinia chrysanthemi during induction chemotherapy followed by consolidation chemotherapy in treating high-risk adults with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma. Asparaginase Erwinia chrysanthemi, a type of protein synthesis inhibitor, is a drug that is made up of the enzyme asparaginase, which comes from the bacterium Erwinia chrysanthemi, and is used with other drugs in people who cannot take asparaginase that comes from the bacterium E. coli. Asparaginase Erwinia chrysanthemi breaks down the amino acid asparagine and may stop the growth of cancer cells that need asparagine to grow. It may also kill cancer cells. Induction therapy, consisting of cytarabine, dexamethasone, vincristine, daunorubicin, methotrexate, and rituximab, is the first choice of treatment. Consolidation therapy, consisting of cyclophosphamide, cytarabine, vincristine, mercaptopurine, methotrexate and rituximab, is given after initial therapy to kill any remaining cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill cancer cells. 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. 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. Cytarabine and mercaptopurine stop cells from making DNA and may kill cancer cells. They are a type of antimetabolite. Daunorubicin blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. It is a type of anthracycline antibiotic and a type of topoisomerase inhibitor. Dexamethasone 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. Giving asparaginase Erwinia chrysanthemi with induction chemotherapy followed by consolidation chemotherapy may be safe, tolerable, and/or effective in treating high-risk adults with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma.

Conditions

B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) (Safety Lead-in)

  Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Will be summarized for evaluable patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.

  Up to completion of induction cycle (cycle length = 28 days)

• Incidence of unacceptable adverse events (Safety Lead-in)

  Will be summarized for evaluable patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.

  Up to completion of induction cycle 1 (cycle length = 28 days)

• Incidence of grade 3 or higher hepatotoxicity and not resolved to grade 1 or lower within 14 days of occurrence (Expansion)

  Will be graded using NCI CTCAE v 5.0. Will be summarized for evaluable patients in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome. The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.

  Up to completion of induction (cycle length = 28 days)

Secondary Outcomes (9)

• Incidence of AEs (Expansion cohort only)

  Up to completion of induction (cycle length = 28 days)

• Composite complete response (CR)

  After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days)

• CR rate

  After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days)

• Minimal residual disease (MRD) negativity

  After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days), at day 28 +/- 42

• MRD negativity

  After consolidation (consolidation cycle length = 8 weeks)

Study Arms (1)

Treatment (asparaginase Erwinia chrysanthemi)

EXPERIMENTAL

See Detailed Description

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Positron Emission Tomography; Biological: Rituximab; Drug: Vincristine Sulfate

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (asparaginase Erwinia chrysanthemi)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and/or biopsy

Treatment (asparaginase Erwinia chrysanthemi)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and/or biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (asparaginase Erwinia chrysanthemi)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (asparaginase Erwinia chrysanthemi)

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 (asparaginase Erwinia chrysanthemi)

Cytarabine DRUG

Given IT

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (asparaginase Erwinia chrysanthemi)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Treatment (asparaginase Erwinia chrysanthemi)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (asparaginase Erwinia chrysanthemi)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (asparaginase Erwinia chrysanthemi)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (asparaginase Erwinia chrysanthemi)

Mercaptopurine DRUG

Given PO

Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, Bw 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785

Treatment (asparaginase Erwinia chrysanthemi)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (asparaginase Erwinia chrysanthemi)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (asparaginase Erwinia chrysanthemi)

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 (asparaginase Erwinia chrysanthemi)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (asparaginase Erwinia chrysanthemi)

Asparaginase Erwinia chrysanthemi DRUG

Given IM

Also known as: 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

Treatment (asparaginase Erwinia chrysanthemi)

Eligibility Criteria

• Age: 18 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

City of Hope at Phoenix

Phoenix, Arizona, 85338, United States

RECRUITING

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

NOT YET RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

NOT YET RECRUITING

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

NOT YET RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

asparaginase erwinia chrysanthemi recombinant; Asparaginase; Specimen Handling; Biopsy; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Spinal Puncture; Mercaptopurine; azathiopurine; Methotrexate; merphos; Magnetic Resonance Spectroscopy; Rituximab; CT-P10; Vincristine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Sulfhydryl Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Ibrahim Aldoss

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

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: April 2, 2025
• First Posted: April 9, 2025
• Study Start: October 10, 2025
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 30, 2029
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

US (8)