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)
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.
• Age ≥ 18 years
• Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor
• AML/MDS relapsed post-alloSCT with measurable residual disease defined by either of the following criteria:
∙ At least 5% or more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall 36
‣ At least 0.1% of abnormal myeloblasts with a leukemia-associated immunophenotype (LAIP) by multiparameter flow cytometry. The abnormal cells with LAIP should not exceed 30% of nucleated cells.
‣ Recurrent or persistent cytogenetic abnormalities detectable by FISH or karyotype analysis.
‣ For patients with mutant NPM1, at least 1,000 mutant transcript copies per 106 ABL or equivalent housekeeping transcripts in bone marrow by qPCR or dPCR
• 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