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.
• 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)