Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

NCT00667277 | Terminated Phase 2 Results DMC

• 3 other identifiers: GCO 07-0548-00103P01CA108671-01A2MPD-RC 103
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Idiopathic; Bevacizumab; Avastin; bone marrow fibrosis; bone marrow angiogenesis; JAK2

Outcome Measures

Primary Outcomes (1)

• Reason for Therapy Discontinuation

  Patient outcomes for myelofibrosis patients treated on a single agent bevacizumab. The two subjects who withdrew consent prior to initiation of therapy are included in the "patient refusal" category.

  2 years

Secondary Outcomes (1)

• Number of Cycles

  2 years

Study Arms (1)

bevacizumab (Avastin)

EXPERIMENTAL

Use of bevacizumab (Avastin) in the treatment of myelofibrosis.

Drug: bevacizumab (Avastin)

Interventions

bevacizumab (Avastin) DRUG

15 mg/kg of bevacizumab by IV infusion once every 3 weeks (1 cycle) for 12 weeks (4 cycles)

Also known as: Avastin

bevacizumab (Avastin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Ronald Hoffman: lead
• Myeloproliferative Disorders-Research Consortium: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Weill Cornell

Ithaca, New York, 14851, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Mesa RA, Silver RT, Verstovsek S, Mascarenhas J, Kessler CM, Rondelli D, Goldberg JD, Marchioli R, Demakos EP, Silverman LR, Hoffman R. Single agent bevacizumab for myelofibrosis: results of the Myeloproliferative Disorders Research Consortium Trial. Haematologica. 2013 Sep;98(9):1421-3. doi: 10.3324/haematol.2012.083337. Epub 2013 Jun 28.

  PMID: 23812932 RESULT

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated due to lack of response activity in the setting of an unacceptable toxicity profile at the completion of the first stage.

Results Point of Contact

• Title: Dr. Ronald Hoffman
• Organization: Icahn School of Medicine at Mount Sinai

ronald.hoffman@mssm.edu

(212) 241-2297

Study Officials

• Ronald Hoffman, MD

  Myeloproliferative Disorders-Research Consortium

  PRINCIPAL INVESTIGATOR

• Ronald Hoffman, MD

  Myeloproliferative Disorders Research Consoritum

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of of Medicine, Hematology and Medical Oncology

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 28, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: August 22, 2014
• Results First Posted: August 22, 2014

Record last verified: 2014-08

Locations

US (5)