Interferon-γ with Donor Leukocyte Infusion for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Donor Stem Cell Transplantation

Inclusion Criteria

• Age ≥ 18 years
• Recipients of an alloSCT for AML or MDS from a minimally 8/8 human leukocyte antigen (HLA)-matched donor
• AML/MDS relapsed post-alloSCT with measurable residual disease defined by at least 5% of more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion
• If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 line of the following: * For hypomethylating agents, venetoclax, and targeted therapies (e.g., tyrosine kinase inhibitors, IDH1/IDH2 inhibitors, or FLT3 inhibitors), the last dose must be > 2 week prior to the initiation of IFN-γ * For cytotoxic chemotherapy agents, the last dose must be > 2 weeks prior to start of treatment for the present study * For investigational agents, the last dose must be ≥ 4 weeks or 5 half-lives (whichever is longer) prior to the start of treatment for the present study
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• For female subject, who is < 55 years old without hysterectomy, oophorectomy or documented menopause, willingness to use two forms of contraception including one form of highly effective contraception (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study
• For male subject, willingness to use highly effective contraception methods including male condoms by male subject and one form of highly effective contraception by his female partner (i.e., long-acting reversible contraception, oral contraceptive pills) for the duration of the study

Exclusion Criteria

• Primary engraftment failure after alloSCT
• Grade 3 or 4 acute graft versus host disease (aGVHD) per Mount Sinai Acute graft versus host disease (GVHD) International Consortium (MAGIC) at the time of planned enrollment
• History of grade 4 aGVHD per the MAGIC criteria
• Moderate or severe chronic (c)GVHD per National Institute of Health (NIH) Consensus Criteria at time of planned enrollment
• Any systemic immunosuppressive medications taken within 2 weeks before the enrollment
• Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment
• A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, Escherichia (E.) coli derived products or any other component of the product
• Positive pregnancy test or currently breastfeeding on day 1 of study treatment
• Active cardiac arrhythmia not controlled by medical management or current New York Heart Association (NYHA) class II or higher congestive heart failure within 2 months of enrollment unless it was due to a tachyarrhythmia which is under control at the time of enrollment
• Active ischemic heart disease not controlled with medications within 2 months of enrollment
• Acute or chronic pulmonary disease requiring continuous oxygen treatment
• Seizure disorder not controlled by medications within 2 months of enrollment
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) or total bilirubin > 3 x ULN at time of enrollment
• Renal function creatinine clearance (CrCl) < 30 mL/min at time of enrollment using modified Cockcroft-Gault formula
• Body surface area ≤ 1.5 m^2 or ≥ 2.5 m^2 so as to minimize variation in IFN-γ exposure based on differences in body surface area