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Anti-TGF-beta Therapy in Patients With Myelofibrosis

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ClinicalTrials.gov Identifier: NCT01291784
Recruitment Status : Terminated (Early termination when the drug was no longer made available by the pharmaceutical company due to unanticipated management and administrative decisions.)
First Posted : February 8, 2011
Results First Posted : August 28, 2014
Last Update Posted : December 8, 2014
Sponsor:
Information provided by (Responsible Party):
John Mascarenhas, Icahn School of Medicine at Mount Sinai

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelofibrosis
Primary Myelofibrosis
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Post-essential Thrombocythemia Related Myelofibrosis
Intervention Biological: monoclonal antibody to TGF-beta
Enrollment 3
Recruitment Details Recruitment period from Jan 2011 to Feb 2012 of known patients to the medical clinic.
Pre-assignment Details  
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description Subject A Subject B Subject C
Period Title: Overall Study
Started 1 1 1
Completed 1 0 1
Not Completed 0 1 0
Arm/Group Title Phase 1 MF Subjects
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
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.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants
68.67  (10.07)
[1]
Measure Description: Actual age
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
2
  66.7%
Male
1
  33.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants
3
1.Primary Outcome
Title Safety and Tolerability
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description:
Subject A
Subject B
Subject C
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: events
4 4 1
2.Secondary Outcome
Title Bauermeister Scale
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description:
Subject A
Subject B
Subject C
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: units on a scale
4 3 4
3.Secondary Outcome
Title European Consensus Fibrosis Grade
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description:
Subject A
Subject B
Subject C
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: units on a scale
3 2 2
4.Secondary Outcome
Title Peripheral Blood CD34+
Hide Description Investigate exploratory markers for their ability to predict responsiveness to treatment with GC1008.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description:
Subject A
Subject B
Subject C
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: percentage of hematopoietic stem cells
3 2 0
5.Secondary Outcome
Title JAK2V617F Allele Burden
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description:
Subject A
Subject B
Subject C
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: percentage of mutant alleles
48 95 14
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sub A Sub B Sub C
Hide Arm/Group Description Subject A Subject B Subject C
All-Cause Mortality
Sub A Sub B Sub C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Sub A Sub B Sub C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/1 (0.00%)      1/1 (100.00%)      0/1 (0.00%)    
Cardiac disorders       
Asystole  1 [1]  0/1 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE
[1]
This event was deemed to not be drug related. Participant progressed to MF
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sub A Sub B Sub C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      1/1 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders       
leukocytosis   0/1 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0
leukopenia   1/1 (100.00%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0
General disorders       
fatigue   0/1 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0
hypoxia   0/1 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0
Immune system disorders       
herpes zoster   0/1 (0.00%)  0 0/1 (0.00%)  0 1/1 (100.00%)  1
Skin and subcutaneous tissue disorders       
skin lesions   1/1 (100.00%)  3 0/1 (0.00%)  0 0/1 (0.00%)  0
Indicates events were collected by systematic assessment

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.

Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. John O. Mascarenhas
Organization: Icahn School of Medicine at Mount Sinai
Phone: 212-241-6756
Responsible Party: John Mascarenhas, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01291784     History of Changes
Other Study ID Numbers: GCO 10-1450
GC1008-JM
First Submitted: February 7, 2011
First Posted: February 8, 2011
Results First Submitted: July 31, 2013
Results First Posted: August 28, 2014
Last Update Posted: December 8, 2014