Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation

Sponsor: Sawa Ito, MD

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT06529731

Patient View

This phase 2 trial evaluates IFN-γ with DLI for relapsed AML/MDS post-alloSCT. Eligible patients must have relapsed AML/MDS, ECOG PS 0-2, and available DLI. Interventions include IFN-γ, a recombinant protein, and DLI, which transfers donor lymphocytes to enhance immune response. The study aims to establish a new treatment standard and explore broader IFN-γ applications.

Patient Parameters

Program Overview

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.

Description

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-emptive post-alloSCT treatment of patients transplanted with measurable residual disease (MRD) or with poor-risk AML/MDS such as with TP53 mutations; and 3) prevention of relapse in patients who can only tolerate reduced-intensity conditioning regimens which in most studies results in higher rates of post-alloSCT AML/MDS relapse than when intensive conditioning regimens are employed. Together, this work would allow more patients with AML/MDS to be referred for and ultimately benefit from an alloSCT.

Eligibility Criteria

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

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