Canakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study

Clonal Cytopenia of Undetermined Significance Clinical Trial

Official title: A Randomized Double-Blind Placebo-Controlled Phase II Multi-Center Study of Inflammation Modification of Canakinumab to Prevent Leukemic Progression of Clonal Cytopenias of Unknown Significance (CCUS): IMPACT Study

Status Recruiting

Clinical Trial Summary

This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the length of time until development of a myeloid neoplasm (ie myelodysplastic syndrome [MDS], myeloproliferative neoplasm [MPN], chronic myelomonocytic leukemia [CMML], or acute myeloid leukemia [AML]) in high-risk clonal cytopenia of undetermined significance (CCUS) patients receiving canakinumab as therapeutic intervention compared to the control arm.

SECONDARY OBJECTIVES:

I. To determine the effect of canakinumab on hematological overall response rate.

II. To determine the effect of canakinumab on complete hematological response rate.

III. To determine the effect of canakinumab on response duration. IV. To determine the effect of canakinumab on overall survival. V. To determine the effect of canakinumab on mutational burden. VI. To determine the effect of canakinumab on infection-related adverse events. VII. To determine the effect of canakinumab on recovery of blood cell populations.

VIII. To determine the effect of canakinumab on cardiovascular episodes compared to a control arm.

IX. Patient reported outcomes will be collected using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C3).

EXPLORATORY OBJECTIVES:

I. To quantify changes in the bone marrow (BM) microenvironment according to immune cell constitution and cytokine levels over the course of canakinumab treatment compared to a control arm.

II. To characterize the inflammatory milieu in peripheral blood (PB) and BM samples by serial measurement and characterization of key cytokines (IL-1, IL-2, IL-6, TNF alpha and beta, and IFN-gamma), sensitivity of patient samples to these cytokines and relationships to various genes involved in clonal hematopoiesis.

III. To determine the dynamics of change in clone size of various CH genes in serial patient treatment and control samples, during the study, by a variety of assays including single cell sequencing, copy number alterations, and variant allele frequency (VAF) measurement to characterize differences in disease evolution.

IV. To collect serial measurement of immune cell populations in PB and BM of serial patient treatment and control samples, during the study, to characterize various immune cells involving both the innate and adaptive immune system including natural killer (NK) cell, T cell subsets namely effector, regulatory and memory T cells as well as various cell surface molecules such as checkpoint modulators (PD-1/PD-L1/TIM-3, LAG-3).

V. To understand the effect of global effects on the BM microenvironment of CH status/post (s/p) canakinumab treatment compared to the control patients using ribonucleic acid (RNA) sequencing and global methylation assays to further characterize unique genomic signatures in these patients.

OUTLINE: Patients are randomized to one of two arms.

ARM I: Patients receive canakinumab subcutaneously (SC) on study.

ARM II: Patients receive placebo SC on study.

All patients also undergo echocardiogram (ECHO) and chest x-ray during screening, collection of blood samples during screening and follow up, and bone marrow biopsy and aspiration throughout the trial. ;

Related Conditions & MeSH terms

• Anemia
• Clonal Cytopenia of Undetermined Significance
• Cytopenia
• Leukopenia
• Thrombocytopenia

• NCT number: NCT05641831
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Contact: The Ohio State University Comprehensive Cancer Center
• Phone: 800-293-5066
• Email: OSUCCCClinicaltrials@osumc.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: February 6, 2023
• Completion date: December 31, 2028