B Acute Lymphoblastic Leukemia, Philadelphia Chromosome NegativePhase 2NCT06918431
Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
A Phase 2 study testing Asparaginase Erwinia chrysanthemi, Biospecimen Collection and Bone Marrow Aspiration in people with B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative and Lymphoblastic Lymphoma, run by City of Hope Medical Center at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 54 years
- Conditions the study is for
- B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Lymphoblastic Lymphoma
- What is being tested?
- Asparaginase Erwinia chrysanthemi, Biospecimen Collection and Bone Marrow Aspiration
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 8 sitesUnited States
- Study dates
- 10 Oct 2025to 30 Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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])
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- 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)
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Wendy Stock, wstock@bsd.uchicago.edu
Wendy Stock
- Not yet recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Anjali S. Advani, advania@ccf.org
Anjali S. Advani
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Ibrahim Aldoss, 626-218-2405, ialdoss@coh.org
Ibrahim Aldoss
- Recruiting
City of Hope at Irvine Lennar
Irvine, California, 92618
Ibrahim Aldoss, 626-218-2405, ialdoss@coh.org
Ibrahim Aldoss
- Not yet recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92093
James K. Mangan, jmangan@ucsd.edu
James K. Mangan
- Not yet recruiting
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Patricia A. Young, pyoung@mednet.ucla.edu
Patricia A. Young
- Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mark B. Geyer, geyerm@mskcc.org
Mark B. Geyer
- Recruiting
City of Hope at Phoenix
Phoenix, Arizona, 85338
Tibor Kovacsovics, MD, 1-888-256-0250, ialdoss@coh.org
About this study
Official title: 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 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of asparaginase Erwinia chrysanthemi (asparaginase Erwinia chrysanthemi-recombinant-rywn [recombinant Erwinia asparaginase]; 25 mg/m^2 every 48 hours [hrs]) as first asparaginase during induction therapy through the assessment of type, frequency, severity, attribution, time course and duration of adverse events. (Safety Lead-in) II. To evaluate the proportion of patients with grade 3 or higher (G3+) hepatotoxicity that are at least possibly related to the study drug (recombinant Erwinia asparaginase) and not resolved to grade 1 or lower within 14 days of occurrence in the target patient population during induction. (Expansion)
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of recombinant Erwinia asparaginase (25 mg/m^2 every 48 hrs) as first asparaginase during induction therapy through the assessment of type, frequency, severity, attribution, and duration of adverse events (expansion cohort).
II. To evaluate composite complete remission (CR or CR with incomplete hematologic recovery [CRi]) rate after induction ± extended induction.
III. To evaluate CR rate after induction ± extended induction. IV. To evaluate minimal residual disease (MRD) negativity rate after induction ± extended induction.
- To evaluate number of patients able to receive extended induction or post induction consolidation or salvage therapy within 42 days from initiating induction.
VI. To evaluate MRD negativity rate after consolidation for patients receiving the study drug.
VII. To evaluate the proportion of patients with G3+ hepatotoxicity that are at least possibly related to the study drug during induction.
VIII. To evaluate the proportion of patients maintaining adequate 48 hour nadir serum asparaginase activity (NSAA ≥ 0.1 IU/mL) post recombinant Erwinia asparaginase during induction +/- extended induction.
IX. To evaluate the duration of G3+ hepatotoxicity.
EXPLORATORY OBJECTIVES:
- To evaluate the safety and tolerability of recombinant Erwinia asparaginase (at approved dosing) as first asparaginase during extended induction and consolidation therapy through the assessment of type, frequency, severity, attribution, time course and duration of adverse events.
II. To evaluate the proportion of patients maintaining adequate, either at 48 hours or 72 hrs, nadir serum asparaginase activity (NSAA ≥ 0.1 IU/mL) post recombinant Erwinia asparaginase during consolidation.
III. To evaluate the molecular profile by next-generation sequencing (NGS) and its association with MRD- response to recombinant Erwinia asparaginase based induction.
OUTLINE:
INDUCTION (CYCLE 1): Patients receive cytarabine intrathecally (IT) on day 1, dexamethasone orally (PO) twice daily (BID) on days 1-7 and 15-21, vincristine intravenously (IV) on days 1, 8, 15, and 22, daunorubicin IV over 5-30 minutes on days 1, 8, 15, and 22, asparaginase Erwinia chrysanthemi intramuscularly (IM) on days 4, 6, 8, 10, 12, 14, and 16, and methotrexate IT on days 8 and 29. Patients with CNS3 disease also receive methotrexate IT on days 15 and 22. CD20 positive patients also receive rituximab IV on day 8. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with M2 marrow (> 5% lymphoblasts) on day 29 proceed to Extended Induction Cycle 1A. All other patients proceed to Consolidation Cycle 2.
EXTENDED INDUCTION (CYCLE 1A): Patients receive dexamethasone PO BID on days 1-7, vincristine IV on days 1 and 8, daunorubicin IV over 5-30 minutes on day 1, and asparaginase Erwinia chrysanthemi IM on days 4, 6, 8, 10, 12, 14, and 16 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION (CYCLE 2): Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50, and methotrexate IT on days 1, 8, 15 and 22 (NOTE: Patients with CNS3 disease omit methotrexate on days 15 and 22). CD20 positive patients also receive rituximab IV on days 1 and 20. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit may also receive asparaginase Erwinia chrysanthemi IM every other day on days 15, 17, 19, 21, 23, 25, 27, 43, 45, 47, 49, 51, 53, and 55 or every Monday/Wednesday/Friday (if days 15 and 43 are Mondays) on days 15, 17, 19, 22, 24, 26, 43, 45, 47, 50, 52, and 54 at discretion of treating physician. Patients may receive 2 courses of every other day or Monday/Wednesday/Friday treatment in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo echocardiography at screening and blood sample collection, bone marrow aspiration and/or biopsy, lumbar puncture, and computed tomography (CT) and/or positron emission tomography (PET)/CT throughout the study.
After completion of study treatment, patients are followed up at 30 days.
- Being tested
- Asparaginase Erwinia chrysanthemi, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography
- Medical subject headings
- Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asparaginase Erwinia chrysanthemiDrug
Also called Asparaginase Erwinia chrysanthemi (Recombinant)-rywn, Asparaginase Erwinia chrysanthemi, Recombinant-rywn, Asparaginase Erwinia chrysanthemi-rywn, Crisantaspase
Given IM
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration and/or biopsy
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow aspiration and/or biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or PET/CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
CytarabineDrug
Also called .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
Given IT
CytarabineDrug
Also called .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
Given IV or SC
Daunorubicin HydrochlorideDrug
Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin
Given IV
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
EchocardiographyProcedure or surgery
Also called EC
Undergo echocardiography
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Undergo lumbar puncture
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IT
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
RituximabBiological
Also called ABP 798, ABP-798, ABP798, BI 695500
Given IV
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (asparaginase Erwinia chrysanthemi) | Experimental | See Detailed Description Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to completion of induction (cycle length = 28 days)
Secondary outcomes (9)
Incidence of AEs (Expansion cohort only)
Will be graded according to 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.
Measured: Up to completion of induction (cycle length = 28 days)
Composite complete response (CR)
Will be defined as CR and CR with incomplete hematologic recovery. The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days)
CR rate
The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days)
Minimal residual disease (MRD) negativity
Will be defined as residual leukemia < 0.01% by flow cytometry and/or clonoSEQ. The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: After induction with or without extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days), at day 28 +/- 42
MRD negativity
The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: After consolidation (consolidation cycle length = 8 weeks)
Proportion of patients to receive extended induction/consolidation/salvage therapy
The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: Within 42 days from initiating induction
Incidence of grade 3 or higher hepatotoxicity
The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: During induction (cycle length = 28 days)
Nadir serum asparaginase activity (NSAA)
Will be defined as NSAA >= 0.1 IU/mL. The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
Measured: At 48 hours post Erwinia asparaginase during induction +/- extended induction (induction cycle length = 28 days, extended induction cycle length = 16 days)
Duration of grade 3 or higher hepatotoxicity
Will be summarized by descriptive statistics (mean, range, etc).
Measured: Time from starting date of the grade 3 or higher hepatoxicity to the resolving (grade ≤ 1) date, assessed up to 30 days after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2025
- Study start10 Oct 2025
- Primary completion30 Mar 2029 (estimated)
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Acute Lymphoblastic Leukemia, Philadelphia Chromosome NegativeStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ibrahim Aldoss, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06918431
- Sponsor's protocol ID
- 24442
- Other IDs
- NCI-2025-02184, 24442, P30CA033572
- Status last verified
- Oct 2026
- First submitted
- 2 Apr 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No