Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML

Inclusion Criteria:

* • Histologically confirmed diagnosis of acute myeloid leukemia (AML) according per 2016 World Health Organization (WHO) criteria.

  * Cluster of differentiation marker (CD)33 and CD123 / interleukin (IL)3RA expression on the subject's blasts, determined by standard Flow AML MRD assay.
  * Age ≥ 12
  * Relapsed or refractory after one cycle of prior therapy (cytoreductive agents such as hydroxyurea, cyclophosphamide, or a single dose of gemtuzumab ozogamicin are not considered prior treatment regimens).
  * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  * Adequate baseline organ function, including cardiac, renal, and hepatic function as defined by:

    * Left ventricular ejection fraction (LVEF) ≥ 50% by multi-gated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to the start of therapy
    * No clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
    * Creatinine Clearance (CrCl) ≥ 60mL/min
    * Serum albumin ≥ 3.2 g/dL (note that albumin infusions are not permitted in order to enable eligibility)
    * Total bilirubin ≤ 1.5 mg/dL
    * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN)
  * white blood cell (WBC) \< 20,000/uL on day of first therapy, cytoreduction may be achieved using hydroxyurea.
  * Ability to understand and willingness to sign a written informed consent document.
  * Able to adhere to study visit schedule and other protocol requirements including follow up for survival assessment.
  * If the patient is a woman of child-bearing potential (WOCBP), they should have a negative serum or urine pregnancy test within 1 week prior to tagraxofusp-erzs treatment. (Note: WOCBP include any female who has experienced menarche and who has not undergone successful sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level ≥ 35 milli-international units per milliliter (mIU/mL).
  * Patients agree to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 1 week after the last tagraxofusp-erzs infusion.
  * The patient has signed informed consent prior to initiation of any study-specific procedures or treatment. The patient is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

* • Prior treatment with tagraxofusp-erzs.

  * Primary resistance to or progression on gemtuzumab. Patients who have previously received Gemtuzumab, but whose disease was not resistant or did not progress on it are eligible.
  * Active central nervous system involvement. Patients with a history of central nervous system involvement that has cleared with prior treatments are eligible.
  * Blood or bone marrow transplant within 60 days of screening or active graft versus host disease.
  * The patient has persistent clinically significant toxicities Grade ≥ 2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
  * The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
  * The patient has an active malignancy and/or cancer history that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease.
  * The patient has clinically significant cardiovascular disease (e.g. uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
  * The patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
  * The patient is receiving immunosuppressive therapy - with the exception of low-dose prednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.
  * The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
  * The patient is pregnant or breastfeeding.
  * The patient has a history of human immunodeficiency virus (HIV) infection, active or chronic Hepatitis B, or Hepatitis C.
  * The patient has any condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities.