Clinical Trial 22367

• Overview

  Study Title:

  The Impact Of Inflammation On HSPC Composition And Disease Progression In Chronic Myelomonocytic Leukemia (CMML INTERCEPT STUDY) SUB-TITLE: Intercepting CMML Disease Progression Driven by Acute Inflammation

  Summary:

  Moffitt Cancer Center is conducting a clinical research study in order to learn more about acute inflammatory events associated with disease progression in participants with Chronic Myelomonocytic Leukemia (CMML).

  Objective:

  STUDY PURPOSE AND HYPOTHESIS 1. Objective and Hypothesis: The short-term goal of this proposal is to demonstrate that acute inflammatory events can precipitate a Mono biased HSPC compartment and that this is associated with disease progression in CMML (Fig 1). We have shown that cytokines are abnormally secreted by leukemia cells and promote their accelerated growth. Our long-term goal is to determine whether early intervention against the cytokine leukemic axis with therapies already tested in CMML will prevent disease progression, thus stabilizing CMML in a clinically asymptomatic state. 2. Study Aims Aim 1: Confirm that Mono biased HSPCs are associated with adverse outcomes and disease progression in a longitudinal cohort CMML study. Rationale: The relationship between inflammation and its biologic impact on CMML is unknown. While anecdotal case reports suggest that acute inflammatory events can lead to disease progression, this concept has not been clinically studied in a prospective fashion. Our preliminary data demonstrates that approximately 1/3 of CMML cases have a Mono biased HSPC composition that may be associated with antecedent inflammatory events. Definitively understanding whether acute inflammatory events lead to Mono biased expansion and disease progression will lay the foundation for interventional studies to mitigate its effect. Therefore, we hypothesize that changes in inflammatory cytokines are a critical microenvironmental mediator of disease progression. One major step in addressing this hypothesis is to determine the chronology between disease progression, inflammatory events, and changes in hematopoietic architecture. Aim 2: Retrospectively determine the prognostic impact of HSPC composition in CMML and other myeloid malignancies. Rationale: Our published data16 suggests that the composition of HSPCs is associated with inflammatory disease progression. However, these data were derived from a small cohort of deeply molecularly characterized samples. To expand and validate these findings, we will leverage Moffitt s existing Flow Cytometry data in which virtually every patient with suspected myeloid malignancy has a limited HSPC characterization. In collaboration with Dr. Ryder in pathology, we will use retrospective flow cytometry data to annotate HSPC composition and correlate this with overall survival. In total, we have over 1000 unique cases with CMML and other myeloid malignancies with flow cytometry and survival data that will be leveraged to validate our findings suggesting the composition of HSPC is associated with progression in leukemia.

• Inclusion Criteria

  • Adults (i.e., 18 years and older)
  • Patients actively enrolled in the Total Cancer Care Protocol (TCC, MCC#14690)
  • Meets definition of clinically asymptomatic state
  • Has no other active malignancy
  • Does not have an uncontrolled infection at the time of study entry
  • Can adhere to monthly standard of care visits
  • Has a WHO-defined diagnosis of CMML.

• Exclusion Criteria

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