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

NCT00410605 | Completed Phase 2 Results DMC

• 7 other identifiers: NCI-2009-00150H-2006-0269CDR0000521546HO064017313U01CA062491P30CA014520
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Multiple Myeloma in Relapse; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bevacizumab and Lenalidomide

  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.

  Up to 5 years

• Progression Free Survival (Time to Progression)

  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.

  up to five years

Secondary Outcomes (4)

• Toxicity and Tolerability of the Bevacizumab and Lenalidomide Combination

  Up to 5 years

• Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline

  Baseline

• Local Cytokine Milieu Using Tissue Micro Arrays of Bone Marrow Biopsy Specimens

  Up to 5 years

• Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline

  Up to Course 4 Day 1 (3 Months Post-baseline)

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: lenalidomide; Drug: dexamethasone

Interventions

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm I

lenalidomide DRUG

Given orally

Also known as: CC-5013, IMiD-1, Revlimid

Arm I

dexamethasone DRUG

Given orally

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Arm I

Eligibility Criteria

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

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bevacizumab; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Natalie Callander
• Organization: Univerisity of Wisconsin Carbone Cancer Center

nsc@medicine.wisc.edu

608-265-8690

Study Officials

• Natalie Callander

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 13, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2014
• Last Updated: September 1, 2017
• Results First Posted: September 1, 2017

Record last verified: 2017-08

Locations

US (2)