Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Myeloproliferative Disorders-Research Consortium
ClinicalTrials.gov Identifier:
NCT00667277
First received: April 24, 2008
Last updated: September 9, 2012
Last verified: September 2012
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

Resource links provided by NLM:


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 ]

Enrollment: 13
Study Start Date: March 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667277

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, New York
Weill Cornell
Ithaca, New York, United States, 14851
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Myeloproliferative Disorders-Research Consortium
Investigators
Principal Investigator: Ronald Hoffman, MD Myeloproliferative Disorders-Research Consortium
Principal Investigator: Ronald Hoffman, MD Myeloproliferative Disorders Research Consoritum
  More Information

No publications provided

Responsible Party: Myeloproliferative Disorders-Research Consortium
ClinicalTrials.gov Identifier: NCT00667277     History of Changes
Other Study ID Numbers: MPD-RC 103, P01 CA 108671-01A2
Study First Received: April 24, 2008
Last Updated: September 9, 2012
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

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

ClinicalTrials.gov processed this record on July 23, 2014