Using interferon-γ and donor cells to treat relapsed leukemia after stem cell transplant

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)

This study is testing if a combination of interferon-γ and donor cells can help people with relapsed leukemia after a stem cell transplant feel better and improve their chances of recovery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (St Louis, Missouri and 2 other locations)
• Trial ID: NCT06529731 on ClinicalTrials.gov

What this trial studies

This phase 2 trial aims to evaluate the effectiveness of interferon-γ combined with donor leukocyte infusion in patients who have relapsed acute myeloid leukemia or myelodysplastic syndromes after receiving an allogeneic hematopoietic stem cell transplant. The study will assess the responsiveness of leukemia cells to interferon-γ both in vitro and in vivo, utilizing single-cell RNA sequencing to analyze the transcriptomic changes in leukemia cell subsets. By confirming the efficacy of this treatment approach, the trial seeks to establish a new standard of care for this high-risk patient population with limited treatment options.

Who should consider this trial

Good fit: Ideal candidates include individuals who have undergone an allogeneic stem cell transplant for acute myeloid leukemia or myelodysplastic syndromes and have experienced a relapse with measurable residual disease.

Not a fit: Patients who have not received an allogeneic stem cell transplant or those with a different type of leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed leukemia after stem cell transplantation.

How similar studies have performed: Previous studies have shown promise with similar approaches, but this specific combination of interferon-γ and donor leukocyte infusion is being tested for the first time in this context.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor
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 myeloblasts with a leukemia-associated immunophenotype (LAIP) by multiparameter flow cytometry. The abnormal cells with LAIP should not exceed 30% of nucleated cells.
   3. Recurrent or persistent cytogenetic abnormalities detectable by FISH or karyotype analysis.
   4. 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
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
5. A DLI is available, or the donor is available and agrees to undergo apheresis to collect lymphocytes for infusion
6. If salvage therapy for post-alloSCT relapse was received, the therapy is limited to 1 line 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
7. Provision of signed and dated informed consent form
8. Stated willingness to comply with all study procedures and availability for the duration of the study
9. 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
10. 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:

1. Primary engraftment failure after alloSCT
2. Grade 3 or 4 aGVHD per Mount Sinai Acute GVHD International Consortium (MAGIC) at the time of planned enrollment
3. History of grade 4 aGVHD per the MAGIC criteria
4. Moderate or severe cGVHD per NIH Consensus Criteria at time of planned enrollment
5. Any systemic immunosuppressive medications taken within 2 weeks before the enrollment
6. Grade 3 or higher non-hematologic toxicity related to any prior therapy at the time of enrollment
7. A contraindication to receive IFN-γ including a known hypersensitivity to IFN-γ, E. coli derived products or any other component of the product
8. Positive pregnancy test or currently breastfeeding on Day 1 of study treatment 37
9. 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
10. Active ischemic heart disease not controlled with medications within 2 months of enrollment
11. Acute or chronic pulmonary disease requiring continuous oxygen treatment
12. Seizure disorder not controlled by medications within 2 months of enrollment
13. AST or ALT \> 5x ULN or total bilirubin \>3x ULN at time of enrollment
14. Renal function CrCl \<30 mL/min at time of enrollment using modified Cockcroft-Gault formula
15. 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

Where this trial is running

St Louis, Missouri and 2 other locations

• Washington University — St Louis, Missouri, United States (Recruiting)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Sawa M Ito, MD, PhD — UPMC Hillman Cancer Center
• Study coordinator: Linda Elias, RN

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes; interferon-γ; donor leukocyte infusion; allogeneic hematopoietic stem cell transplantation