Status:
RECRUITING
Interferon-γ (IFN-γ) With Donor Leukocyte Infusion to Treat Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes Post Allogeneic Hematopoietic Stem Cell Transplantation
Lead Sponsor:
Sawa Ito, MD
Collaborating Sponsors:
Evans MDS Discovery Research Grant
Amgen
Conditions:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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...
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 effic...
Eligibility Criteria
Inclusion
- 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
- 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
- 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
Key Trial Info
Start Date :
September 23 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 31 2027
Estimated Enrollment :
45 Patients enrolled
Trial Details
Trial ID
NCT06529731
Start Date
September 23 2024
End Date
October 31 2027
Last Update
October 14 2025
Active Locations (3)
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1
Washington University
St Louis, Missouri, United States, 63110
2
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
3
Fred Hutchinson Cancer Center
Seattle, Washington, United States, 98109