Phase I/II Clinical Trial of Axatilimab, a CSF1R Monoclonal Antibody, in Combination With Ruxolitinib as Therapy for Patients With Myelofibrosis (MF) and Chronic Myelomonocytic Leukemia (CMML)

Description

Primary Objectives:

* Phase 1 dose escalation: to determine safety, tolerability and Maximum Tolerated Dose (MTD) and efficacy of axatilimab alone and in combination with ruxolitinib for patients with MF and CMML
* Phase 2 dose expansion: to determine the overall response rate (ORR) of axatilimab and ruxolitinib in patients with MF and CMML.
* Incidence of AEs, MTD and changes in clinical laboratory values.
* Measures of efficacy in CMML: overall response rate (ORR) defined as sum of CR + complete cytogenetic remission + partial remission + marrow response + clinical benefit according to the IWG 2015 MDS/MPN response criteria37.
* Measures of efficacy in MF: objective response which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after 6 cycles of treatment. It will be categorized according to the International Working Group (IWG) consensus criteria for myelofibrosis26

Secondary Objectives:

CMML:

* To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall survival (OS).
* To evaluate symptom burden improvement assessed by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS).
* To evaluate changes in clonal composition and VAF of identified mutations with therapy
* To measure changes in cytokine profile and monocyte populations in peripheral blood and bone marrow.

MF:

* To explore time to response and duration of response
* To explore changes in bone marrow fibrosis
* To evaluate symptom burden improvement assessed by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS) (Appendix 1).
* To explore changes in dynamic of cytogenetics and molecular mutations: JAK2V617F, CALR, MPL (or other relevant molecular markers) in terms of allele burden or changes in cytogenetic abnormalities
* To measure changes in serum and bone marrow cytokine profile pre- and post-therapy