Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)

Inclusion Criteria:

* A histologically or pathologically confirmed diagnosis of AML based on 2016 WHO classification. Patients with Complex Karyotype AML (CK-AML) and TP53-mutated AML are eligible for this study.
* AML has relapsed after or is refractory to, first-line therapy, with a maximum of three prior lines of therapy. Patients whose AML has FLT3 or IDH1/IDH2 mutations should have received at least one available FLT3 or IDH1/IDH2 inhibitors
* Age 18 years and older
* ECOG performance status ≤ 2
* Patients who have undergone allo-HSCT are eligible if they are ≥ 30 days post stem cell infusion, have no evidence of graft versus hose disease ( GVHD ) \> Grade 1, and are ≥ 10 days off all immunosuppressive therapy
* Previous cytotoxic chemotherapy must have been completed at least 10 days prior to day 1 of treatment on the study and all AEs (excluding alopecia, acne, rash) due to agents administered earlier should have recovered to \< Grade 1. Patients with hematologic malignancies are expected to have hematologic abnormalities at study entry. These abnormalities which are thought to be primarily related to the underlying leukemia, are not considered to be toxicities (AE) and do not need to resolve to \< Grade 1
* All biologic agents including hematopoietic growth factors must have been stopped at least 1 week prior to day 1 of treatment on the study
* Patients must have adequate organ function as defined below:

  * Direct bilirubin ≤2X the institutional upper limit of normal (ULN) (except in patients with leukemic infiltration of the liver)
  * AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of the liver)
  * Alkaline phosphatase ≤5X ULN
  * Creatinine Clearance (CrCl) ≥ 45 mL/min (except in patients with evidence of tumor lysis syndrome)
  * Patients with a history of CNS leukemia must be stable with clear CSF for \> 2 months prior to day 1 of treatment (patient can receive intrathecal maintenance chemotherapy)
* Female patients of childbearing potential must have a negative pregnancy test \<1 week prior to enrollment. Female patients of childbearing potential who are sexually active and male patients who are sexually active and have female partners of childbearing potential must agree to use highly effective method of contraception with their partners during exposure to study drugs and for 30 days after the last dose of study drugs.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy
* Patients with acute promyelocytic leukemia (APL) confirmed with t(15;17) (i.e. FAB subtype M3 and M3 variant)
* Prior treatment with any asparaginase product. Patients who received ≤12 weeks of a BCL-2 inhibitor including venetoclax are eligible.
* Absolute peripheral blast \> 100,000/μL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The decision to start hydroxyurea during this time is at the discretion of the treating physician.
* Patients with the following clinical histories are excluded:

  * severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis is defined by lipase elevation \>5X ULN and with signs or symptoms
  * unprovoked deep venous thrombosis (DVT)
  * pulmonary emboli
  * hemorrhagic or thromboembolic stroke
  * other malignancies requiring systemic chemotherapy, immunotherapy or targeted therapy in the last three months
* Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements
* Pregnant women and female patients who are lactating and do not agree to stop breast- feeding.
* Uncontrolled active seizure
* Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study