Flotetuzumab in Primary Induction Failure (PIF) or Early Relapse (ER) Acute Myeloid Leukemia (AML)

Inclusion Criteria

• Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification
• Patients with AML must meet one of the following criteria, a or b:
• Primary Induction Failure (PIF) AML, defined as disease refractory to either, i or ii:
• i. An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. Examples include but are not limited to: 1 cycle of high dose cytarabine (HiDAC) containing regimen, 1 cycle of liposomal cytarabine and daunorubicin, 2 cycles of standard dose cytarabine containing regimen
• ii. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens: i ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine, or ii ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy
• Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration < 6 months
• Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): up to 2 induction (induction, re-induction) or 1 induction plus/minus 1 consolidation attempt, followed by a maximum of 1 salvage/re-induction attempt.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Life expectancy of at least 4 weeks
• Peripheral blast count </= 20,000/mm3 at the time of first dose
• Acceptable laboratory parameters and adequate organ reserve

Exclusion Criteria

• History of allogeneic stem cell transplantation
• Prior treatment with an anti-CD123-directed agent
• Need for concurrent other cytoreductive chemotherapy
• Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation)
• Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.
• Antitumor therapy or investigational agent within 14 days or 5 half-lives of Cycle 1 Day 1.
• Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, otic preparations, nasal spray or ophthalmic solution
• Use of immunosuppressant medications in the 2 weeks prior to Cycle 1 Day 1
• Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to Cycle 1 Day 1
• Known central nervous system (CNS) leukemia
• Active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection),
• Known human immunodeficiency virus infection, unless all of the following criteria are met: CD4+ count ≥ 350 cells/μL, undetectable viral load, and receiving highly active antiretroviral therapy.
• Known, active, history of or current acute or chronic hepatitis B or C virus (HBV) infection (as evidenced by detectable HBV surface antigen and HBV DNA ≥ 500 IU/mL),
• History of hepatitis C virus (HCV) infection, unless the infection has been treated and cured,
• Active SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing for ongoing infection should follow local clinical practice guidelines/standards. Participants with a positive test result for ongoing SARS-CoV-2 infection, known asymptomatic infection, or suspected infection are excluded unless or until asymptomatic and with subsequent negative SARS-CoV-2 laboratory test.