Recruiting Phase 2

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

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About this study

This phase 2 study aims to confirm the efficacy observed in the prior phase 1 trial in Cohort 1 and to evaluate the safety of IFN-γ in combination with DLI in Cohort 2, the haploidentical donor alloSCT recipient cohort. The study will 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 assess whether leukemia blasts are responsive to IFN-γ in vitro and in vivo. Single-cell RNA sequencing (scRNAseq) will be performed to evaluate transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.

Condition: Acute Myeloid Leukemia, Myelodysplastic Syndromes
Tested: Interferon gamma-1b, Donor Leukocyte Infusion (DLI)
Sponsor: Sawa Ito, MD

Who can join

Age: 18 years and older
Sex: All sexes
Healthy volunteers: Not accepted

Inclusion 19

Minimum age: 18 years
Study condition: Acute Myeloid Leukemia, Myelodysplastic Syndromes
Age ≥ 18 years
Recipients of an alloSCT for AML or MDS from a minimally 8/8 HLA-matched donor (Cohort 1: HLA -matched alloSCT recipients) or recipients of a haploidentical donor SCT for AML or MDS from a minimally 4/8 HLA-matched donor (Cohort 2: Haplo-SCT recipients)
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 16

Primary engraftment failure after alloSCT
Evidence of mixed phenotype leukemia with lymphoid differentiation (Cohort 1: HLA -matched alloSCT recipients)
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
Detection of HLA loss of heterozygosity (LOH) in relapsed malignant cells. Specifically, there has been a loss of the mismatched set of HLA alleles encoded on chromosome 6 (ie uniparental disomy of chromosome 6), within 30 days prior to enrollment (Cohort 2: Haplo-SCT recipients)

Where

3 sites, 3 recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Recruiting

Washington University

St Louis, Missouri, United States

Recruiting

Contact

Linda Elias, RN

412-623-6037 eliaslj@upmc.edu
Amy Rodger, RN

412-623-4036 rodgax@upmc.edu

Potential match only. Final eligibility is determined by the study team.