This phase I trial tests the safety, side effects and best dose of decoy-resistant interleukin-18 (DR-18) and how well it works in treating patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has come back after a period of improvement (relapsed) or that remains despite treatment (persistent) after hematopoietic cell transplantation (HCT). HCT is the only curative therapy for most forms of AML and MDS. However, relapse occurs in a third of patients and is the most common cause of death after HCT. DR-18, a variant of the human cytokine interleukin-18, binds to IL-18 binding probein (IL-18BP) and overcomes the inhibitory effect of the IL-18BP on IL-18, which may boost the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving DR-18 may be safe, tolerable and/or effective in treating patient with relapsed or persistent AML or MDS after HCT.
≥ 18 years of age (no upper age limit)
The most recent HCT was from a 10/10 human leukocyte antigen (HLA)-matched related or unrelated donor (assessed at HLA-A, B, C, DR, DQ)
Evidence of blood count recovery at any time post-HCT defined as absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L for ≥ 3 consecutive days and platelets ≥ 30 x 10^9/L (independent of granulocyte colony-stimulating factor [G-CSF] or platelet transfusions for 5 days). (Blood count recovery may not be sustained.)
Absent, stable or reducing immune suppression in the preceding 4 weeks without GvHD flares
Cellular immunotherapy or new targeted therapy in the 4 weeks prior to the first DR-18 injection
History of grade 3 or 4 acute GvHD after the most recent HCT
History of moderate or severe chronic GvHD after the most recent HCT
Active acute or chronic GvHD or other immunologic phenomenon (e.g., immune cytopenias, cryptogenic immunologic pneumonia) in last month requiring systemic therapy (Hydrocortisone or prednisone for adrenal insufficiency at ≤ 10 mg/day prednisone-equivalent is permitted.)
Single group
Decoy-resistant interleukin-18
Biological/VaccineGiven SC
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Number of subjects who complete a minimum of 2 doses within 4 consecutive weeks of DR-18
Occurrence of dose-limiting toxicities (DLTs)
DLTs will be defined as the dosing scheme associated with a true DLT rate of ≤ 25%. DLTs will be recorded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
Composite complete response (CR)
Composite CR will be assessed according to European LeukemiaNet 2022 criteria.
Partial response (PR)
PR will be defined as 25% reduction in blasts in subjects with morphologic disease pre-DR-18 treatment. Response will be assessed according to European LeukemiaNet 2022 criteria.
Overall response rate (ORR)
ORR will be defined as composite CR + PR in subjects with morphologic disease pre-DR-18 treatment. ORR will be determined using European LeukemiaNet 2022 response criteria.
Minimal residual disease (MRD) negativity
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Fred Hutchinson Cancer Center
Lead sponsor
Simcha Therapeutics
Collaborator
