Bevacizumab, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Stage II or Stage III Multiple Myeloma

Refractory Multiple Myeloma Clinical Trial

Official title:

Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00410605
• Other study ID #: NCI-2009-00150
• Secondary ID: NCI-2009-00150H-
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 11, 2006
• Last updated: April 9, 2014
• Start date: November 2006

Study information

• Verified date: April 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well giving bevacizumab together with lenalidomide and dexamethasone works in treating patients with relapsed or refractory stage II or stage III multiple myeloma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Dexamethasone may stimulate the immune system in different ways and stop cancer cells from growing. Giving bevacizumab together with lenalidomide and dexamethasone may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. Determine the overall response rate (complete response and partial response) in patients with relapsed or refractory stage II or III multiple myeloma treated with bevacizumab, lenalidomide, and dexamethasone.

SECONDARY OBJECTIVES:

I. Determine time to progression in these patients. II. Determine the toxicity and tolerability of this regimen. III. Determine the effect of bevacizumab and lenalidomide on markers of myeloma activity in myeloma cells and stromal cells, including interleukin-6, macrophage inflammatory protein-1α, vascular endothelial growth factor, and STAT3.

IV. Assess local cytokine milieu using tissue microarrays of bone marrow biopsy specimens.

OUTLINE: This is a multicenter, open-label study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral lenalidomide on days 1-21, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and before courses 2 and 4. Blood samples are examined for vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms by pyrosequencing and VEGF, VEGFR1, VEGFR2, interleukin-6, and macrophage inflammatory protein 1 by immunoenzyme techniques. Relationships between plasma cell myeloma and stroma and the effect of study treatment on these relationships are examined in tissue sections of bone marrow before and after treatment utilizing microvessel density measurements, VEGF staining, and STAT3 staining (by immunohistochemistry and fluorescent in situ hybridization [FISH]).

After completion of study treatment, patients are followed periodically for at least 5 years.

Other known NCT identifiers

• NCT00406328

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed symptomatic multiple myeloma:

• Stage II or III disease

• Relapsed or refractory disease after >= 2 courses of prior chemotherapy

• Measurable levels of monoclonal protein (M protein) > 1.0 g/dL by serum protein electrophoresis OR > 200 mg of monoclonal light chain by 24-hour urine protein electrophoresis

• Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest diameter to be recorded) >= 20 mm with conventional techniques OR >= 10 mm with spiral CT scan (for patients with lytic bone disease)

• No known brain metastases

• ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%

• Patients with PS of 3 are eligible if it is due to pain that is likely to improve with treatment

• Life expectancy > 6 months

• No known HIV positivity

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• No active infections requiring oral or intravenous antibiotics within the past week

• No proteinuria (i.e., albuminuria) > 1,000 mg/24 hours unless related to the diagnosis of multiple myeloma

• Patients with light chain (i.e., "Bence-Jones") proteinuria are still eligible if the non-light chain component of protein is < 1,000 mg/24 hours

• No serious nonhealing wound or ulcer

• No blood pressure > 150/90 mm Hg (even with medication)

• No significant traumatic injury within the past 28 days

• No clinically significant peripheral vascular disease

• No evidence of bleeding diathesis or coagulopathy

• No unstable angina or myocardial infarction within the past 6 months

• No stroke within the past 6 months

• No New York Heart Association class III or IV heart failure

• No secondary malignancy within the past 2 years except squamous cell or basal cell carcinoma of the skin or carcinoma in situ of the cervix

• Hemoglobin > 9 g/dL (may be supported by transfusion or growth factors)

• WBC >= 2,000/mm^3

• Absolute neutrophil count >= 1,000/mm^3

• Platelet count >= 75,000/mm^3

• Bilirubin =< 2.5 mg/dL

• At least 4 weeks since prior chemotherapy or radiotherapy and recovered

• More than 7 days since prior minor surgical procedures, fine-needle aspirations, or core biopsies:

More than 24 hours since prior bone marrow biopsy or central veinous access placement

• More than 28 days since prior major surgical procedure or open biopsy

• At least 4 weeks since prior and no concurrent participation in another experimental drug study

• Prior autologous peripheral blood stem cell transplantation allowed

• No prior lenalidomide

• Concurrent full-dose anticoagulants allowed provided all of the following criteria are met:

• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• No thrombocytopenia requiring transfusion

• Platelet count > 75,000/mm3

• INR 2-3 and stable

• No concurrent major surgery

• No concurrent sargramostim (GM-CSF)

• No other concurrent investigational agents

• No other concurrent anticancer agents or therapies

• AST and ALT =< 5 times upper limit of normal

• Creatinine < 2.5 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and 4 weeks after completion of study treatment

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to lenalidomide and/or bevacizumab or other agents used in the study

Study Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Biological:
• bevacizumab
Given IV

Drug:
• lenalidomide
Given orally
• dexamethasone
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed anti-tumor response rate (complete response and partial response) to the combination of bevacizumab and lenalidomide	Responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). Furthermore, two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be computed using the method proposed by Chang, which takes into account the multiplicity problem associated with the two-stage testing procedure. The objective response rate will be estimated by using Whitehead's bias-adjustment approach.	Up to 5 years	No
Secondary	Time to progression (TTP)	TTP will be summarized using point estimates of the median time to progression and associated 95% confidence intervals. The data will be presented graphically using Kaplan-Meier plots. Exploratory analysis, including multivariate Cox regression with demographic variables and markers of myeloma activity as covariates, may be performed.	The number of days from the day of first drug administration to the day the patient experiences an event of disease progression or death, assessed up to 5 years	No
Secondary	Type and severity of toxicity incidents of the bevacizumab/lenalidomide combination summarized using NCI Common Toxicity Criteria	Ninety percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) will be constructed.	Up to 5 years	Yes