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

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

NCT ID: NCT06529731

Condition: Acute Myeloid Leukemia
Myelodysplastic Syndromes

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Interferons
Interferon-gamma

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

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Interferon gamma-1b
Description: 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.
Arm group label: IFN-γ + DLI

Other name: ACTIMMUNE®

Intervention type: Biological
Intervention name: Donor Leukocyte Infusion (DLI)
Description: 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.
Arm group label: IFN-γ + DLI

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.

Detailed 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.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: UPMC Hillman Cancer Center

Address:
City: Pittsburgh
Zip: 15232
Country: United States

Status: Recruiting

Contact:
Last name: Linda Elias, RN

Phone: 412-623-6037
Email: eliaslj@upmc.edu

Contact backup:
Last name: Amy Rodger, RN

Phone: 412-623-4036
Email: rodgax@upmc.edu

Investigator:
Last name: Sawa Ito, MD, PhD
Email: Principal Investigator

Start date: August 22, 2024

Completion date: October 31, 2027

Lead sponsor:
Agency: Sawa Ito, MD
Agency class: Other

Collaborator:
Agency: Evans MDS Discovery Research Grant
Agency class: Other

Collaborator:
Agency: Amgen
Agency class: Industry

Collaborator:
Agency: FDA Office of Orphan Products Development
Agency class: U.S. Fed

Source: University of Pittsburgh

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06529731