Post-transplant Flotetuzumab for AML

Prior treatment

• 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
• Previous or known hypersensitivity to biological agents or constituents of flotetuzumab or its source material
• Concurrent use of any other investigational drugs
• 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

Other illness

• Patients with active, uncontrolled infection. If an infection is controlled and under treatment, then the patient may become eligible.
• Uncontrolled infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV)

Lab values

• Inadequate end organ function defined as:
  • Hepatic-AST, ALT, and alkaline phosphatase \> 3.5X upper limit of normal (ULN), bilirubin \>2.5X ULN
  • Renal-creatinine clearance \<60 mL/min using the modified Cockcroft-Gault formula
  • Cardiac-Recent myocardial infarction within 6 months, Congestive Heart Failure with ejection fraction (EF) \<50%, active pericarditis or myocarditis
  • Pulmonary-Need for supplemental oxygen to maintain oxygen saturation \>92%
  • Adrenal-Adrenal insufficiency requiring physiologically-dosed steroids

Other

• No evidence of donor engraftment (100% patient 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
• Women who are pregnant or lactating

• A confirmed prior diagnosis of AML and underwent an alloHSCT as a form of consolidation in a morphologic complete remission
• 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 T4 within the reference range, or a TSH below the reference range with both a free T4 and total 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/mm3 at time of initiation on Cycle 1 Day 1