A Phase 2 Trial of Interferon-γ (IFN-γ) in Combination With Donor Leukocyte Infusion (DLI) to Treat Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) After Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT)

Description

This phase 2 study aims to confirm the efficacy seen in the prior phase 1 trial, and further contribute to this effort through the collection of leukemia cells pre- and post- in vivo IFN-γ therapy. As in the previously conducted phase 1 trial, this trial will test whether leukemia blasts were responsive to IFN-γ in vitro and in vivo, with single-cell RNA sequencing (scRNAseq) conducted to understand the transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.This novel regimen has the potential to fill a large unmet need for this high-risk population of patients who have few, if any, effective therapeutic options. If this trial confirms the clinical efficacy of IFN-γ/DLI, it will establish a new standard of care for post-transplant AML/MDS relapse. It would also provide a rationale to explore other indications for IFN-γ in the context of an alloSCT, including 1) IFN-γ/DLI for relapsed disease after haploidentical alloSCT; 2) pre-

Trial Eligibility

Inclusion Criteria: * Recipients of an alloSCT for AML or MDS from an 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 cycle of the following: 1. 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 2. For cytotoxic chemotherapy agents, the last dose must be \>2 weeks prior to start of treatment for the present study 3. 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 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment * History of grade 4 aGVHD per the MAGIC criteria * Moderate or severe cGVHD per 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, 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 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 * AST or ALT \> 5x ULN or total bilirubin \>3x ULN at time of enrollment * Renal function eGFR \<30 mL/min at time of enrollment using modified Cockcroft-Gault formula * Body surface area ≤ 1.5 m2 or ≥ 2.5 m2 so as to minimize variation in IFN-γ exposure based on differences in body surface area

Study Info

Interventions

Locations Recruiting

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