Trial Outcomes & Findings for Anti-TGF-beta Therapy in Patients With Myelofibrosis (NCT NCT01291784)

NCT ID: NCT01291784

Last Updated: 2014-12-08

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

28 days

Results posted on

2014-12-08

Participant Flow

Recruitment period from Jan 2011 to Feb 2012 of known patients to the medical clinic.

Participant milestones

Participant milestones
Measure
Sub A
Subject A
Sub B
Subject B
Sub C
Subject C
Overall Study
STARTED
1
1
1
Overall Study
COMPLETED
1
0
1
Overall Study
NOT COMPLETED
0
1
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anti-TGF-beta Therapy in Patients With Myelofibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Phase 1 MF Subjects
n=3 Participants
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.
Age, Continuous
68.67 years
STANDARD_DEVIATION 10.07 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
Region of Enrollment
United States
3 participants
n=5 Participants

PRIMARY outcome

Timeframe: 28 days

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.

Outcome measures

Outcome measures
Measure
Sub A
n=1 Participants
Subject A
Sub B
n=1 Participants
Subject B
Sub C
n=1 Participants
Subject C
Safety and Tolerability
4 events
4 events
1 events

SECONDARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure
Sub A
n=1 Participants
Subject A
Sub B
n=1 Participants
Subject B
Sub C
n=1 Participants
Subject C
Bauermeister Scale
4 units on a scale
3 units on a scale
4 units on a scale

SECONDARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure
Sub A
n=1 Participants
Subject A
Sub B
n=1 Participants
Subject B
Sub C
n=1 Participants
Subject C
European Consensus Fibrosis Grade
3 units on a scale
2 units on a scale
2 units on a scale

SECONDARY outcome

Timeframe: 6 months

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

Outcome measures

Outcome measures
Measure
Sub A
n=1 Participants
Subject A
Sub B
n=1 Participants
Subject B
Sub C
n=1 Participants
Subject C
Peripheral Blood CD34+
3 percentage of hematopoietic stem cells
2 percentage of hematopoietic stem cells
0 percentage of hematopoietic stem cells

SECONDARY outcome

Timeframe: 6 months

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.

Outcome measures

Outcome measures
Measure
Sub A
n=1 Participants
Subject A
Sub B
n=1 Participants
Subject B
Sub C
n=1 Participants
Subject C
JAK2V617F Allele Burden
48 percentage of mutant alleles
95 percentage of mutant alleles
14 percentage of mutant alleles

Adverse Events

Sub A

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Sub B

Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths

Sub C

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Sub A
n=1 participants at risk
Subject A
Sub B
n=1 participants at risk
Subject B
Sub C
n=1 participants at risk
Subject C
Cardiac disorders
Asystole
0.00%
0/1
100.0%
1/1 • Number of events 1
0.00%
0/1

Other adverse events

Other adverse events
Measure
Sub A
n=1 participants at risk
Subject A
Sub B
n=1 participants at risk
Subject B
Sub C
n=1 participants at risk
Subject C
Blood and lymphatic system disorders
leukocytosis
0.00%
0/1
100.0%
1/1 • Number of events 1
0.00%
0/1
General disorders
fatigue
0.00%
0/1
100.0%
1/1 • Number of events 1
0.00%
0/1
General disorders
hypoxia
0.00%
0/1
100.0%
1/1 • Number of events 1
0.00%
0/1
Blood and lymphatic system disorders
leukopenia
100.0%
1/1 • Number of events 1
0.00%
0/1
0.00%
0/1
Skin and subcutaneous tissue disorders
skin lesions
100.0%
1/1 • Number of events 3
0.00%
0/1
0.00%
0/1
Immune system disorders
herpes zoster
0.00%
0/1
0.00%
0/1
100.0%
1/1 • Number of events 1

Additional Information

Dr. John O. Mascarenhas

Icahn School of Medicine at Mount Sinai

Phone: 212-241-6756

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place