Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

Myelofibrosis Clinical Trial

Official title:

Phase II Study of Bevacizumab (Avastin®) in Myelofibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00667277
• Other study ID #: GCO 07-0548-00103
• Secondary ID: P01CA108671-01A2
• Status: Terminated
• Phase: Phase 2
• First received: April 24, 2008
• Last updated: August 8, 2014
• Start date: March 2008
• Est. completion date: March 2010

Study information

• Verified date: August 2014
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

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

Locations

Country	Name	City	State
United States	University of Illinois at Chicago	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Weill Cornell	Ithaca	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Georgetown University	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Ronald Hoffman	Myeloproliferative Disorders-Research Consortium, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & 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. Haem — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Number of Cycles	Number of cycles of bevacizumab received. Patients received bevacizumab as a single agent at a dose of 15 mg/kg intravenously on Day 1 of a 21-day cycle.	2 years	No