This study involves Vyxeos (CPX-351), a formulation of a fixed combination of the two anti-tumor drugs, cytarabine and daunorubicin that will be given as an infusion over 90 minutes. This study will use what is called a "liposome" injection. This is a special fat capsule (called a liposome) that surrounds the cytarabine and daunorubicin and protects the drugs from being eliminated/destroyed by the body.

Inclusion Criteria:

• Willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Able to adhere to the study visit schedule and other protocol requirements.
• Pathologically confirmed B- or T-cell acute lymphoblastic or mixed phenotype acute leukemia, with >5% peripheral blood or bone marrow lymphoblasts and/or extramedullary disease >1x1cm.
• Relapsed or refractory acute lymphoblastic leukemia after at least 1 prior cycle of therapy. Patients with Philadelphia chromosome positive disease must have failed at least two prior tyrosine kinase inhibitors.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Cardiac ejection fraction ≥ 50% by echocardiography or multigated acquisition scan (MUGA).
• Must be at least 2 weeks out from any prior systemic chemotherapy, blinatumumab, radiation, and/or other investigational agents, and have recovered to grade 1 from any toxicity related to prior therapy. Glucocorticoids are permitted up to 1 day prior to the first dose.
• Serum bilirubin and creatinine less than 1.5x upper limit of normal (ULN). AST and ALT must be less than 3x ULN, unless there is suspected liver involvement.
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening. A FCBP is considered when a sexually mature female: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months.
• A FCBP must agree to use of two methods of highly effective contraception, be surgically sterile, or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study treatment.
• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 30 days after the last dose of study therapy. Men must agree to not donate sperm during and after the study

Exclusion Criteria:

• Clinical evidence of active central nervous system (CNS) leukemia.
• Any major surgery or radiation therapy within four weeks.
• Any active infection requiring systemic therapy, including HIV, Hepatitis B, and/or Hepatitis C.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator (including but not limited to severe graft-versus-host disease, unstable angina, pulmonary hypertension, active/prior veno-occlusive disease of the liver or severe CHF (NYHA III-IV).
• Patients with active (uncontrolled, metastatic) second malignancies.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 after the last dose of trial treatment.
• Hypersensitivity to cytarabine, daunorubicin, or liposomal products.
• History of Wilson's disease or other copper-metabolism disorder.
• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m^2 daunorubicin or equivalent).

Adverse events were collected from the time of consent until 30 days after the last dose of CPX-351, approximately 34 months.