Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation
NCT Number: NCT06529731
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Acute Myeloid Leukemia|Myelodysplastic Syndromes
Interventions: DRUG: Interferon gamma-1b|BIOLOGICAL: Donor Leukocyte Infusion (DLI)
Sponsor: Sawa Ito, MD
Collaborators: Evans MDS Discovery Research Grant|Amgen
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 45
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-22
Completion Date: 2027-08-31
Locations: UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 15232, United States

Summary:
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.

Primary Outcome Measures: Event-free survival (EFS), Occurrence of treatment failure, hematologic relapse from a CR (complete remission)/CRh/Cri), or death observed from start of IFN-γ treatment. Patients alive at 1 year after start of treatment will be censored on the date of last contact., At 1 year
Secondary Outcome Measures: Event-free survival (EFS) - Landmark 1-year, Time from start of IFN-γ treatment until event of death, date of treatment failure, or hematologic relapse from a CR/CRh/Cri. CR is defined by blasts less than 5% by morphology defined by bone marrow blasts less than 5%; absence of circulating blasts; absence of extramedullary disease; absolute neutrophil count (ANC) at or greater than 1,000/mL; platelet count at or greater than 100,000/mL CRh is defined by ANC at or greater than 500/mL and platelet count at or greater than 50,000/mL otherwise all other CR criteria met. CRi is defined by all CR criteria except for residual neutropenia less than 1,000/mL or thrombocytopenia less than 100,000/mL Treatment failure is not achieving either CR, CRh or CRi by 6 months. Patients evaluable for response without CR, CRh or CRi by 6 months and patients who die before 6 months without response assessments are considered an event at day 1 of IFN-γ treatment, Up to 1 year|Minimal residual disease (MRD), Rate of complete remission (CR) with no measurable disease at 6 months. CR is defined as, At 6 months|Complete Remission (CR), Proportion of patients who experience Complete Remission (CR). CR is defined by bone marrow blasts less than 5%; absence of circulating blasts; absence of extramedullary disease; absolute neutrophil count (ANC) at or greater than 1,000/mL; platelet count at or greater than 100,000/mL. The proportion of responders will be calculated as the number of responders divided by the number of evaluable patients., At 6 months|Complete remission with partial hematologic recovery (CRh), Proportion of patients who experience Complete remission with partial hematologic recovery (CRh). CRh is defined by ANC at or greater than 500/mL and platelet count at or greater than 50,000/mL otherwise all other CR criteria met. The proportion of responders will be calculated as the number of responders divided by the number of evaluable patients., At 6 months|Complete remission with incomplete count recovery (CRi), Proportion of patients who experience complete remission with incomplete count recovery (CRi). CRi is defined by all CR criteria except for residual neutropenia less than 1,000/mL or thrombocytopenia less than 100,000/mL51. The proportion of responders (CR, CRh, or CRi) will be calculated as the number of responders divided by the number of evaluable patients. The proportion of responders will be calculated as the number of responders divided by the number of evaluable patients., At 6 months|Overall survival, Time from start of IFN-γ to death by any cause or censored on the date of last contact., Up to 1 year|Rate of donor chimerism, Proportion of the efficacy population with ≥95% peripheral blood CD3+ and CD33+ cells and of unfractionated bone marrow being donor-derived, At 6 months|Rate of transfusion independence, Proportion of the subjects who achieve the absence of a red-cell or platelet transfusion for at least 56 days between the first and last day of treatment., At 1 year|Frequency and severity of adverse events (AEs), Number of patients who experience an Adverse Event or Serious Adverse Event related to study treatment, per CTCAE v5.0 criteria. Distinct number of patients will be determined per each event type by highest grade experienced., Up to 6 months|Frequency of new onset grade 3 or 4 acute graft-versus-host disease (aGVHD), number of patients meeting criteria for grade 3 or 4 aGVHD per MAGIC divided by the number of evaluable patients. The MAGIC criteria as follows: Overall clinical grade (based on most severe target organ involvement): Grade 0: No stage 1-4 of any organ; Grade I: Stage 1-2 skin without liver, upper GI, or lower GI involvement; Grade II: Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI; Grade Ill: Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 upper GI; Grade IV: Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI., Up to 12 months|Frequency of new onset moderate or severe chronic GVDH (cGVHD), The number of patients meeting criteria for moderate or severe cGVHD per NIH Consensus Criteria divided by the number of evaluable patients. The NIH Consensus Criteria is a diagnostic assessment that evaluates hair, skin, nails, eyes, mouth, genitalia, GI tract, liver, lung, muscles and joints, hematopoietic and immune system, cardiac and neurological condition/function, to determine whether or not the GVHD is chronic., Up to 12 months