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Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis
This study is currently recruiting participants.
Verified by Myeloproliferative Disorders-Research Consortium, January 2009
First Received: April 24, 2008   Last Updated: January 14, 2009   History of Changes
Sponsored by: Myeloproliferative Disorders-Research Consortium
Information provided by: Myeloproliferative Disorders-Research Consortium
ClinicalTrials.gov Identifier: NCT00667277
  Purpose

Myelofibrosis is the gradual replacement of bone marrow (place where most new blood cells are produced) by fibrous tissue which reduces the body's ability to produce new blood cells and results in the development of chronic anemia (low red blood cell count). One of the main distinctions of myelofibrosis is "extramedullary hematopoiesis", the migration or traveling of the blood-forming cells out of the bones to other parts of the body, such as the liver or spleen, resulting in an enlarged spleen and liver.

There is not a standard treatment for myelofibrosis, therefore there is no medication that is specifically used in the treatment of myelofibrosis.

Bevacizumab (Avastin®) targets and stops a growth factor in the body that helps produce the type of fibrous tissue that is gradually replacing the bone marrow in the bones.

The purpose of this study is to find out how safe and effective bevacizumab is in treating myelofibrosis. The investigators also wish to find out important biologic characteristics or features of myelofibrosis (how it works and operates) during the time of study participation through an additional correlative biomarker study (MPD-RC #107). The purpose of the biomarker study is to understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases, while the main study is trying to find out how well bevacizumab will work in treating the disease.


Condition Intervention Phase
Myelofibrosis
Drug: bevacizumab (Avastin)
Phase II

MedlinePlus related topics: Spleen Diseases
Drug Information available for: Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

Further study details as provided by Myeloproliferative Disorders-Research Consortium:

Primary Outcome Measures:
  • To determine the safety and efficacy of bevacizumab treatment in patients with idiopathic myelofibrosis (IM) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate pertinent biologic characteristics of IM before and during the therapy with bevacizumab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 34
Study Start Date: March 2008
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Use of bevacizumab (Avastin) in the treatment of myelofibrosis.
Drug: bevacizumab (Avastin)
15 mg/kg of bevacizumab by IV infusion once every 3 weeks (1 cycle) for 12 weeks (4 cycles)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of primary myelofibrosis, essential thrombocythemia related myelofibrosis, and polycythemia vera related myelofibrosis requiring therapy, including those previously treated and relapsed or refractory, or, if newly diagnosed, with intermediate or high risk according to Lille scoring system
  • Patients not willing to undergo, not a candidate for, or not having a donor for a bone marrow transplant.
  • Signed informed consent: Patients must have signed consents for both the bevacizumab protocol and for the mandatory biomarker MDP-RC 107 protocol to be eligible to participate.
  • Patients must have been off any IM-directed therapy for 2 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy.
  • Serum bilirubin levels less than or equal to 2 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed by treating physician to active hemolysis or ineffective erythropoiesis due to myelofibrosis;
  • Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels less than or equal to 2x ULN.
  • Serum creatinine levels less than or equal to 1.5 x ULN.
  • Women of childbearing potential must have a negative serum or urine pregnancy test prior to bevacizumab treatment and should be advised to avoid becoming pregnant. Men must be advised to not father a child while receiving treatment with bevacizumab. Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures). Women of child bearing potential are women who are not menopausal for 12 months or who have not undergone previous surgical sterilization.
  • Age > 18 years.
  • LVEF >50% by MUGA or ECHO (only in patients with prior exposure to anthracyclines).

Exclusion Criteria:

  • Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Inadequately controlled hypertension (defined as systolic blood pressure >140 and/or diastolic blood pressure >90 mmHg on antihypertensive medications) within 4 weeks prior to entering this study
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • Unstable angina
  • History of myocardial infarction within 6 months
  • History of stroke or transient ischemic attack within 6 months
  • History of Budd-Chiari Syndrome or portal vein thrombosis.
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or clinically significant coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days, or anticipation of the need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device or bone marrow biopsy, within 7 days prior to study enrollment
  • Proteinuria at screening as demonstrated by either

    • Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening OR
    • Urinalysis with proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months
  • Ongoing serious, non-healing wound, ulcer, or bone fracture
  • Known hypersensitivity to any component of bevacizumab
  • Patients with a history of DVT and/or a CNS thrombotic or hemorrhagic event within the past 6 months.
  • Patients on anticoagulation therapy for a variety of conditions such as prosthetic heart valves or chronic atrial fibrillation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667277

Contacts
Contact: Ronald S Hoffman, MD (212) 241-2297 ronald.hoffman@mssm.edu
Contact: Srdan S Verstovsek, MD, PhD (713) 745-3429 sverstov@mdanderson.org

Locations
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Principal Investigator: Craig Kessler, MD            
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Principal Investigator: Damiano Rondelli, MD            
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Principal Investigator: Ronald Hoffman, MD            
Weill Cornell Recruiting
Ithaca, New York, United States, 14851
Principal Investigator: Richard Silver, MD            
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Srdan Verstovsek            
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84102
Principal Investigator: Joseph Prachal, MD            
Sponsors and Collaborators
Myeloproliferative Disorders-Research Consortium
Investigators
Study Chair: Ronald Hoffman, MD Myeloproliferative Disorders-Research Consortium
  More Information

No publications provided

Responsible Party: MyeloproliferativeDRC ( Ronald Hoffman, MD - Study Chair )
Study ID Numbers: MPD-RC 103, P01 CA 108671-01A2
Study First Received: April 24, 2008
Last Updated: January 14, 2009
ClinicalTrials.gov Identifier: NCT00667277     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Myeloproliferative Disorders-Research Consortium:
Myelofibrosis
Idiopathic
Bevacizumab
Avastin
bone marrow fibrosis
bone marrow angiogenesis
JAK2

Study placed in the following topic categories:
Myeloid Metaplasia
Lymphatic Diseases
Myelofibrosis
Hematologic Diseases
Fibrosis
Metaplasia
Myeloproliferative Disorders
Bevacizumab
Bone Marrow Diseases
Angiogenesis Inhibitors

Additional relevant MeSH terms:
Myelofibrosis
Antineoplastic Agents
Hematologic Diseases
Growth Substances
Physiological Effects of Drugs
Myeloproliferative Disorders
Bevacizumab
Angiogenesis Inhibitors
Pharmacologic Actions
Myeloid Metaplasia
Lymphatic Diseases
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Bone Marrow Diseases
Splenic Diseases

ClinicalTrials.gov processed this record on May 07, 2009