A Phase 1/1b Study Evaluating Asparaginase Erwinia Chrysanthemi- Recombinant-Rywn (Recombinant Erwinia Asparaginase) and Venetoclax in Combination With Blinatumomab in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
This phase I/Ib trial tests the safety and side effects of asparaginase Erwinia chrysanthemi-recombinant-rywn (recombinant Erwinia asparaginase) and venetoclax in combination with blinatumomab and how well the combination works in treating patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). 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. It is used 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. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a drug used to treat certain types of B-cell acute lymphoblastic leukemia that are CD19 positive (expresses the protein CD19). Blinatumomab binds to CD19, which is found on most B cells (a type of white blood cell) and some types of leukemia cells. It also binds to a protein called CD3, which is found on T cells (another type of white blood cell). This may help the immune system kill cancer cells. Blinatumomab is a type of bispecific T-cell engager. Giving asparaginase Erwinia chrysanthemi and venetoclax in combination with blinatumomab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory ALL.
• Documented informed consent of the participant and/or legally authorized representative
• Age between 12 and 55
• Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS) ≥ 70
• Patients with relapsed or refractory (R/R) CD19 positive (+) B-cell acute lymphoblastic leukemia (B-ALL) according to World Health Organization (WHO) criteria
⁃ Greater than or equal to 5% blasts in the bone marrow
• White blood cell count less than 25 x 10\^9/L prior to initiation of venetoclax. (within 14 days prior to day 1 of protocol therapy) Cytoreduction with hydroxyurea, steroid or a single dose of cyclophosphamide 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 underlying leukemia, ≤ 3 x ULN)
• Prothrombin time (PT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
• Partial thromboplastin time (PTT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 14 days prior to day 1 of protocol therapy) (Unless it is related to underlying leukemia, then AST ≤ 5 x ULN)
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 14 days prior to day 1 of protocol therapy) (Unless it is related to underlying leukemia, then ALT ≤ 5 x ULN)
• 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)
• Left ventricular ejection fraction (LVEF) ≥ 50% (within 14 days prior to day 1 of protocol therapy)
⁃ Note: Echocardiogram to be performed within 42 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 method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
⁃ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).