TGF-β is a cytokine that is found to be upregulated in the bone marrow of patients with myelofibrosis. This cytokine likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The investigators propose that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation. This is a novel approach to the treatment of patients with myelofibrosis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
starting dose of 1mg/kg intravenous over approximately 1 hour every 4 weeks for a total of 6 doses
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Safety and Tolerability
To assess the safety and tolerability of GC1008 in patients with primary myelofibrosis (PMF) or post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF). A total of 9 AEs determined by the investigator to be at least possibly related to GC1008 occurred during the study.
Time frame: 28 days
Bauermeister Scale
To assess the clinical response to therapy with GC1008 by International Working Group (IWG) criteria and measure the change in degree of bone marrow fibrosis (BMF) assessed by Bauermeister scale. Bauermeister scale: 0, no demonstrable reticulin fibers; 1, occasional fine individual fibers and foci of a fine-fiber network; 2, fine fiber network throughout most of the section, but no coarse fibers; 3, diffuse fiber network with scattered thick coarse fibers, but no mature collagen; and 4, diffuse, often coarse fiber network with areas of collagen.
Time frame: 6 months
European Consensus Fibrosis Grade
To assess the clinical response to therapy with GC1008 by International Working Group (IWG) criteria and measure the change in degree of bone marrow fibrosis (BMF) assessed by European consensus grading system. This scheme consists of a qualitative (reticulin or collagen) and quantitative evaluation of bone marrow fibrosis and distinguishes four increasing categories, ranging from MF-0, which corresponds to normal bone marrow, to MF-3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Time frame: 6 months
Peripheral Blood CD34+
Investigate exploratory markers for their ability to predict responsiveness to treatment with GC1008.
Time frame: 6 months
JAK2V617F Allele Burden
Investigate exploratory markers, hematopoietic cells, for their ability to predict responsiveness to treatment with GC1008. Analysis of percentage of mutant alleles in hematopoietic stem cells.
Time frame: 6 months
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