Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Camurati-Engelmann Disease

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

starting dose of 1mg/kg intravenous over approximately 1 hour every 4 weeks for a total of 6 doses

monoclonal antibody to TGF-beta

John Mascarenhas, MD

Ronald Hoffman, MD

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.

Anti-TGF-beta Therapy in Patients With Myelofibrosis

Phase I Study of GC1008 in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera/Essential Thrombocythemia Related Myelofibrosis (Post-PV/ET MF)

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.

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.

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.

Investigate exploratory markers for their ability to predict responsiveness to treatment with GC1008.

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.

John Mascarenhas

Principal Investigator

Sub A

Sub B

Sub C

3 subjects were enrolled in the study. The three subjects were treated at a GC1008 dose level of 1 mg/kg given intravenously over approximately 60 minutes and then repeated every 28 days for a total of 6 cycles in the core study period and then an additional 6 cycles in an extension phase.

Phase 1 MF Subjects

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

patients with intermediate -1 or higher primary myelofibrosis (PMF) or post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF). Patients were eligible if they had documented BMF of MF-2 or higher as assessed by the European consensus grading score and grade 3 or higher by modified Bauermeister scale.

Early termination when the drug was no longer made available by the pharmaceutical company due to unanticipated management and administrative decisions.

Limited patient data (2 evaluable patients), a dose accumulation ratio cannot be determined.

Spots Global Cancer Trial Database for Anti-TGF-beta Therapy in Patients With Myelofibrosis

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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