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.
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
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
Single group
Asparaginase Erwinia chrysanthemi
DrugGiven IM
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration and/or biopsy
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and/or biopsy
Computed Tomography
Procedure/SurgeryUndergo CT or PET/CT
Cyclophosphamide
DrugGiven IV
Cytarabine
DrugGiven IT
Cytarabine
DrugGiven IV or SC
Daunorubicin Hydrochloride
DrugGiven IV
Dexamethasone
DrugGiven PO
Echocardiography
Procedure/SurgeryUndergo echocardiography
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Mercaptopurine
DrugGiven PO
Methotrexate
DrugGiven IT
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Rituximab
Biological/VaccineGiven IV
Vincristine Sulfate
DrugGiven IV
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.
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.
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.
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.
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.
CR rate
The overall rate and its 95% Clopper Pearson binomial confidence interval (CI) will be estimated.
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.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
