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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00410605
First received: December 11, 2006
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Biological: bevacizumab
Drug: lenalidomide
Drug: dexamethasone
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed anti-tumor response rate (complete response and partial response) to the combination of bevacizumab and lenalidomide [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to progression (TTP) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Type and severity of toxicity incidents of the bevacizumab/lenalidomide combination summarized using NCI Common Toxicity Criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Ninety percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) will be constructed.


Enrollment: 39
Study Start Date: November 2006
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: lenalidomide
Given orally
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: dexamethasone
Given orally
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00410605

Locations
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Natalie Callander University of Wisconsin Hospital and Clinics
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00410605     History of Changes
Obsolete Identifiers: NCT00406328
Other Study ID Numbers: NCI-2009-00150, NCI-2009-00150, H-2006-0269, CDR0000521546, HO06401, HO06401, 7313, U01CA062491, P30CA014520
Study First Received: December 11, 2006
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Thalidomide
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bevacizumab
Lenalidomide
BB 1101
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on July 29, 2014