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

NCT06529731 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HCC 23-1601R01FD008187-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Keywords

interferon-γ (IFN-γ); donor leukocyte infusion (DLI); allogeneic hematopoietic stem cell transplantation (alloSCT)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Event-free survival (EFS) - Landmark 1-year

  Up to 1 year

• Minimal residual disease (MRD)

  At 6 months

• Complete Remission (CR)

  At 6 months

• Complete remission with partial hematologic recovery (CRh)

  At 6 months

• Complete remission with incomplete count recovery (CRi)

  At 6 months

Study Arms (1)

IFN-γ + DLI

EXPERIMENTAL

ACTIMMUNE® (IFN-γ-1b) at a dose of 50 mcg/m\^2 (All participants will receive a 4-week period of IFN-γ monotherapy with ACTIMMUNE 100 mcg 3 times a week. This dose and schedule will be continued for 4 additional weeks and then tapered to 100 mcg weekly for an additional 4 weeks) DLI at a dose of 10\^7 CD3+ cells/kg (DLI doses will be given pending clinical assessment for disease, graft versus host disease (GVHD) and peripheral blood donor chimerism the week prior to DLI. Second DLI dose is only offered to subjects with residual disease not requiring cytotoxic therapy and without GVHD)

Drug: Interferon gamma-1b; Biological: Donor Leukocyte Infusion (DLI)

Interventions

Interferon gamma-1b DRUG

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.

Also known as: ACTIMMUNE®

IFN-γ + DLI

Donor Leukocyte Infusion (DLI) BIOLOGICAL

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.

IFN-γ + DLI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 37
• 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 CrCl \<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

Sponsors & Collaborators

• Sawa Ito, MD: lead
• Evans MDS Discovery Research Grant: collaborator
• Amgen: collaborator
• FDA Office of Orphan Products Development: collaborator

Study Sites (3)

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

interferon gamma-1b

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Sawa M Ito, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linda Elias, RN

CONTACT

412-623-6037; eliaslj@upmc.edu

Amy Rodger, RN

CONTACT

412-623-4036; rodgax@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 31, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)