DR-18 for the Treatment of Relapsed or Persistent Acute Myeloid Leukemia or Myelodysplastic Syndrome After Hematopoietic Cell Transplantation, the DR. DREAM Trial
NCT Number: NCT06492707
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Acute Myeloid Leukemia|Myelodysplastic Syndrome|Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome
Interventions: BIOLOGICAL: Decoy-resistant interleukin-18|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration
Sponsor: Fred Hutchinson Cancer Center
Collaborators: Simcha Therapeutics
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 20
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-01
Completion Date: 2027-05-01
Locations: Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, 98109, United States

Summary:
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.

Primary Outcome Measures: Number of subjects who complete 4 consecutive weeks of DR-18, At the end of week 4|Incidence 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., Up to 6 weeks after first dose of DR-18, or 2 weeks after the last induction dose of DR-18, whichever is later
Secondary Outcome Measures: Composite complete response (CR), Composite CR will be assessed according to European LeukemiaNet 2022 criteria., At 1 month after the first dose of DR-18|Partial response (PR), PR will be defined as 25% reduction in blasts in subjects with morphologic disease at enrollment. Response will be assessed according to European LeukemiaNet 2022 criteria., At 1 month after first dose of DR-18|Overall response rate (ORR), ORR will be defined as composite CR + PR in subjects with morphologic disease at enrollment. ORR will be determined using European LeukemiaNet 2022 response criteria., At 1 month after the first dose of DR-18|Minimal residual disease negativity, At 1 month after the first dose of DR-18|Overall survival (OS), OS will be assessed with the Kaplan-Meier method., At 6 months and at 12 months after first dose of DR-18|Incidence of grade 2 and grade 3-4 acute graft versus host disease (GVHD), Cumulative incidence estimates will be obtained for outcomes with competing risks., From first DR-18 injection up to 6 months after the last injection|Incidence of moderate to severe chronic GVHD, Cumulative incidence estimates will be obtained for outcomes with competing risks., At 6 months after the first DR-18 injection|Incidence of grade 1-4 cytokine release syndrome (CRS), Incidence of grade 1-4 CRS will be graded using the American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome grading system., Up to 4 weeks after the last dose of DR-18|Incidence of neutropenia, Neutropenia will be defined as absolute neutrophil count (ANC) \< 500/uL for \> 14 days not attributed to disease progression or other cause, assessable in subjects with ANC ≥ 500/uL and no granulocyte colony-stimulating factor receipt in the prior 100 days at time of first DR-18 injection., Up to 4 weeks after the last dose of DR-18|Incidence of thrombocytopenia, Thrombocytopenia will be defined as platelets \< 20 K/uL for \> 14 days not attributed to disease progression or other cause, assessable in subjects with platelets ≥ 20 K/uL and no platelet transfusion in the prior 7 days at time of first DR-18 injection., Up to 4 weeks after the last dose of DR-18|Incidence of other grade 3-5 adverse events (AEs), AEs will be recorded using NCI CTCAE v5.0., Up to 4 weeks after the last DR-18 injection