- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00410605
Bevacizumab, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Stage II or III Multiple Myeloma
Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma
Study Overview
Status
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Cancer Institute
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Hospital and Clinics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm I
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.
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Given IV
Other Names:
Given orally
Other Names:
Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bevacizumab and Lenalidomide
Time Frame: Up to 5 years
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Patient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria).
Responses were 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 were 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 was estimated by using Whitehead's bias-adjustment approach.
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Up to 5 years
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Progression Free Survival (Time to Progression)
Time Frame: up to five years
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Patient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria).
Progression free survival was summarized using point estimates of the median time to progression and associated 95% confidence intervals.
The data was presented graphically using Kaplan-Meier plots.
Exploratory analysis, including multivariate Cox regression with demographic variables and markers of myeloma activity as covariates was performed.
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up to five years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity and Tolerability of the Bevacizumab and Lenalidomide Combination
Time Frame: Up to 5 years
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Adverse events/toxicities were collected during regular clinical visits.
Confidence intervals for the estimate of the true number of patients suffereing from grade 3 or 4 toxicities per common terminology criteria were calculated using the Wilson interval.
Ninety-five percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) were constructed.
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Up to 5 years
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Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
Time Frame: Baseline
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A Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients.
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Baseline
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Local Cytokine Milieu Using Tissue Micro Arrays of Bone Marrow Biopsy Specimens
Time Frame: Up to 5 years
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Up to 5 years
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Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
Time Frame: Up to Course 4 Day 1 (3 Months Post-baseline)
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A Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients.
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Up to Course 4 Day 1 (3 Months Post-baseline)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natalie Callander, University of Wisconsin, Madison
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dexamethasone
- Antibodies
- Lenalidomide
- Immunoglobulins
- Bevacizumab
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
Other Study ID Numbers
- NCI-2009-00150 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA014520 (U.S. NIH Grant/Contract)
- U01CA062491 (U.S. NIH Grant/Contract)
- H-2006-0269 (Other Identifier: UW Health Sciences IRB)
- CDR0000521546
- HO06401 (Other Identifier: University of Wisconsin Hospital and Clinics)
- 7313 (CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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