Flotetuzumab for the Treatment of Patients with Relapsed/Refractory CD123+ Acute Myeloid Leukemia Following an Allogeneic Stem Cell Transplant

Inclusion Criteria

• A confirmed prior diagnosis of AML and underwent an alloHSCT as a form of consolidation in a morphologic complete remission
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Ability to give informed consent
• In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
• Age ≥ 18 years
• Prior treatment with a CD123-targeted therapy will be allowed assuming the patient did not have a grade 3 or 4 adverse reaction to prior use of this treatment
• Normal thyroid function (defined by either a thyroid stimulating hormone [TSH] within the reference range, a TSH above the reference range with a free thyroxine [T4] within the reference range, or a TSH below the reference range with both a free T4 and total triiodothyroinine [T3] within the reference range) or normal thyroid tests on supplementation or treatment (defined as a TSH within the reference range)
• Patients should be at least 30 days from transplant with morphologic evidence of disease progression on bone marrow biopsy
• The presence of a CD123+ AML must be confirmed by flow cytometry with > 1% CD123 AML blasts
• Peripheral blast count =< 20,000/mm^3 at time of initiation on cycle 1 day 1

Exclusion Criteria

• No evidence of donor engraftment (100% patient deoxyribonucleic acid [DNA] in bone marrow or peripheral blood after alloHSCT based on either an unsorted specimen or CD3 sorted)
• Active AML in central nervous system (CNS) or testes
• Patients with active, uncontrolled infection. If an infection is controlled and under treatment, then the patient may become eligible
• Patients with active acute or chronic GVHD requiring GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
• Patients without active acute or chronic GVHD requiring prophylactic GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
• Aspartate aminotransferase (AST) > 3.5 X upper limit of normal (ULN)
• Alanine aminotransferase (ALT) > 3.5 X ULN
• Alkaline phosphatase > 3.5 X ULN
• Bilirubin > 2.5 X ULN
• Creatinine clearance < 60 mL/min using the modified Cockcroft-Gault formula
• Recent myocardial infarction within 6 months
• Congestive heart failure with ejection fraction (EF) < 50%
• Active pericarditis or myocarditis
• Need for supplemental oxygen to maintain oxygen saturation > 92%
• Adrenal insufficiency requiring physiologically-dosed steroids
• Women who are pregnant or lactating
• Previous or known hypersensitivity to biological agents or constituents of flotetuzumab or its source material
• Concurrent use of any other investigational drugs
• Uncontrolled infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV)
• Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave’s disease now euthyroid clinically with stable supplementation)
• Previous treatment with radiotherapy or an immunotherapeutic agent in the 14 days prior to study drug administration (cycle 1 day 1) or 5 half-lifes, whichever is longer
• Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or equivalent, except steroid inhaler, nasal spray, or ophthalmic solution
• Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration
• Prior adverse event with CD123 therapy necessitating therapy discontinuation