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MyelofibrosisPhase 1NCT01291784

Anti-TGF-beta Therapy in Patients With Myelofibrosis

A Phase 1 study testing monoclonal antibody to TGF-beta in people with Myelofibrosis and Primary Myelofibrosis, run by John Mascarenhas at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
monoclonal antibody to TGF-beta
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Feb 2011to Jan 2013
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18
  • ECOG 0-2
  • Intermediate-1 or higher by IWG-MRT Post PV/ET MF patients OR intermediate-1 or higher JAK2V617F negative PMF
  • Bone marrow MF-2 or higher as assessed by the European consensus grading score AND grade 3 or higher by modified Bauermeister scale.
  • Patients must be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney.
  • Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the investigational agent, and for at least 3 months after the last treatment.
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  • At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (except hydroxyurea) immunotherapy, or biotherapy/targeted therapies and recovered from the toxicity of prior treatment to < Grade 1, exclusive of alopecia. Concurrent cancer therapy is not permitted for the exception of hydroxyurea if already being used at a stable dose for 3 weeks prior to screening.
  • Patients must have negative tests for human immunodeficiency virus (HIV) and for hepatitis viruses B and C (antibody and/or antigen) unless the result is consistent with prior vaccination or prior infection with full recovery.
  • Marrow: Absolute neutrophil count ≥ 500/mm3, and platelet count ≥50,000/mm3 without the need for platelet transfusion within 4 weeks
  • Hepatic: Serum total bilirubin >1.5 X upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if their total bilirubin is >3.0 mg/dL); alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >2.5 X ULN.
  • Renal: Serum creatinine of < 1.5 x upper limit of normal (ULN) or, if higher, estimated or measured creatinine clearance >45 mL/min.
  • Coagulation:
  • Prothrombin Time (PT) < 1.5 X ULN
  • Partial thromboplastin time (aPTT) < 1.5 X ULN

Who cannot join

  • Central nervous system (CNS) cancer or metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
  • Pregnant or nursing women, due to the unknown effects of GC1008 on the developing fetus or newborn infant.
  • Patients with known bleeding diathesis or signs of uncontrolled active bleeding (hematuria, GI bleeding) other than self-limited causes of benign etiology that have been adequately investigated at the discretion of the investigator.
  • Patients requiring anticoagulation with aspirin > 81mg daily, unfractionated heparin, low molecular weight heparin (LMWH), direct anti-thrombin inhibitors, or vitamin K antagonists (e.g. warfarin). This does not apply to patients actively receiving aspirin at a dose of ≤ 81mg a day.
  • Patients diagnosed with another malignancy - unless following curative intent therapy, the patient has been disease free for at least 5 years and the probability of recurrence of the prior malignancy is >5%. Patients with curatively treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are eligible for this study.
  • Patients with an organ transplant, including those that have received an allogeneic bone marrow transplant.
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  • Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks if the treatment was with a long-acting agent such as a monoclonal antibody).
  • Significant or uncontrolled medical illness, such as congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with a remote history of asthma or active mild asthma may participate.
  • Active autoimmune disorders or concurrent immunosuppressive medications such as prednisone, interferon, cyclosporine, methotrexate or azathioprine.
  • Active infection requiring antibiotics.
  • A known allergy to any component of GC1008.
  • Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to:
  • Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs.
  • Any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

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

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.

Being tested
monoclonal antibody to TGF-beta
Keywords
monoclonal antibody
Medical subject headings
Primary Myelofibrosis, Polycythemia Vera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • monoclonal antibody to TGF-betaBiological

    Also called GC1008

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

Study groups in NCT01291784
Study groupRoleWhat they receive
monoclonal antibody to TGF-betaExperimentalstarting dose of 1mg/kg intravenous over approximately 1 hour every 4 weeks for a total of 6 doses
Receives: Biological: monoclonal antibody to TGF-beta

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

Secondary outcomes (4)

  1. 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.

    Measured: 6 months

  2. 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.

    Measured: 6 months

  3. Peripheral Blood CD34+

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

    Measured: 6 months

  4. 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.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2011 (estimated)
  2. Study startFeb 2011
  3. Primary completionJan 2013
  4. Study completionJan 2013

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

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01291784
Sponsor's protocol ID
GCO 10-1450
Other IDs
GC1008-JM
Status last verified
Nov 2014
First submitted
7 Feb 2011
Last updated
8 Dec 2014
Data monitoring committee
Yes

Publications

  • Mascarenhas J, Li T, Sandy L, Newsom C, Petersen B, Godbold J, Hoffman R. Anti-transforming growth factor-beta therapy in patients with myelofibrosis. Leuk Lymphoma. 2014 Feb;55(2):450-2. doi: 10.3109/10428194.2013.805329. Epub 2013 Jun 24. No abstract available.

    PubMed 23682558

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing monoclonal antibody to TGF-beta in people with Myelofibrosis and Primary Myelofibrosis, run by John Mascarenhas at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01291784, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2014.

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