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)
Sawa Ito, MD
Summary
This phase 2 study aims to confirm the efficacy observed in the prior phase 1 trial in Cohort 1 and to evaluate the safety of IFN-γ in combination with DLI in Cohort 2, the haploidentical donor alloSCT recipient cohort. The study will 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 assess whether leukemia blasts are responsive to IFN-γ in vitro and in vivo. Single-cell RNA sequencing (scRNAseq) will be performed to evaluate transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.
Description
This novel regimen has the potential to address a significant unmet need for this high-risk population of patients who have few, if any, effective therapeutic options. In Cohort 1, if this trial confirms the clinical efficacy of IFN-γ/DLI in patients with relapsed AML/MDS after HLA-matched alloSCT, it may establish a new therapeutic approach for post-transplant AML/MDS relapse. Cohort 2 will further evaluate the safety and potential efficacy of IFN-γ/DLI in patients with relapsed AML/MDS after haploidentical alloSCT, where treatment options are also limited and the risk of GVHD requires carefu…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Age ≥ 18 years 2. Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor (Cohort 1: HLA -matched alloSCT recipients) or recipients of a haploidentical donor SCT for AML or MDS from a minimally 4/8 HLA-matched donor (Cohort 2: Haplo-SCT recipients) 3. AML/MDS relapsed post-alloSCT with measurable residual disease defined by either of the following criteria: 1. At least 5% or more myeloblasts based on bone marrow biopsy morphology by pathologist review. Abnormal myeloblasts cannot not exceed 30% overall 36 2. At least 0.1% of abnormal myelob…
Interventions
- DrugInterferon gamma-1b
ACTIMMUNE/Interferon gamma-1b is a single-chain polypeptide containing 140 amino acids that is produced by fermentation of a genetically engineered Escherichia coli bacterium containing the DNA which encodes for the recombinant protein. Interferon gamma-1b is part of a drug regimen used to treat Chronic Granulomatous Disease, or CGD. CGD is a genetic disorder, usually diagnosed in childhood, that affects some cells of the immune system and the body's ability to fight infections effectively.
- BiologicalDonor Leukocyte Infusion (DLI)
Donor lymphocyte infusion is a procedure that transfers healthy white blood cells (lymphocytes) from a bone marrow or stem cell donor to a recipient's blood. An infusion of healthy lymphocytes helps the recipient's immune system get rid of remaining cancer cells if they have a relapse after a bone marrow or stem cell transplant for blood cancer.
Locations (3)
- Washington UniversitySt Louis, Missouri
- UPMC Hillman Cancer CenterPittsburgh, Pennsylvania
- Fred Hutchinson Cancer CenterSeattle, Washington