Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma

March 12, 2009 updated by: Fred Hutchinson Cancer Center

A Phase II Trial With VELCADE® (PS-341), Cytoxan (Cyclophosphamide), Dexamethasone and Thalomid® (VEL-CTD) in Previously Untreated Multiple Myeloma Patients

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide works in treating patients with newly diagnosed, previously untreated multiple myeloma.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the response rate in patients with newly diagnosed, previously untreated multiple myeloma treated with bortezomib, cyclophosphamide, dexamethasone, and thalidomide.

Secondary

  • Determine the safety and tolerability of this regimen in these patients.

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

Patients receive bortezomib IV on days 1, 4, 8, and 11; cyclophosphamide IV on days 1 and 8 of courses 1-3; oral thalidomide once daily on days 1-21 beginning in course 4; and dexamethasone IV or orally once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Comprehensive Cancer Center
      • Los Angeles, California, United States, 90048
        • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
      • Palm Springs, California, United States, 92262
        • Desert Regional Medical Center Comprehensive Cancer Center
      • Sacramento, California, United States, 95816
        • Sutter Cancer center
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
    • New York
      • New York, New York, United States, 10011
        • St. Vincent's Comprehensive Cancer Center - Manhattan
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University Cancer Institute
    • Texas
      • Austin, Texas, United States, 78759
        • Lone Star Oncology - Austin
    • Washington
      • Seattle, Washington, United States, 98109-1023
        • Seattle Cancer Care Alliance
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma meeting 1 of the following criteria:

    • Monoclonal immunoglobulin spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL) and kappa or lambda light chain excretion > 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:

      • Bone marrow plasmacytosis (10-30% plasma cells)
      • Lytic bone lesions

    • Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:

      • Lytic bone lesions
      • IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

    • Bone marrow plasmacytosis (> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:

      • Monoclonal immunoglobulin of lesser magnitude present
      • Lytic bone lesions
      • IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
    • FreeLite testing abnormal and kappa:lambda light chain ratio abnormal

  • Symptomatic disease requiring treatment

    • Documented related organ or tissue involvement, if present

  • Measurable disease, defined as 1 of the following:

    • Monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/day
    • Abnormal FreeLite testing (for nonsecretors)

    • Patients with nonsecretory disease must meet either of the following criteria for measurability:

      • Has measurable protein by FreeLite testing
      • Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow
  • Newly diagnosed, previously untreated disease
  • No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
  • No plasma cell leukemia

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 50-100%

  • Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ if bone marrow is extensively infiltrated)

    • Extensive infiltration is defined as > 50% myeloma cells or plasma cells
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophil count ≥ 1,500/mm³
  • AST and ALT ≤ 2 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN (unless clearly related to the disease)
  • Creatinine clearance ≥ 20 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective contraception ≥ 4 weeks prior to beginning treatment, during, and for ≥ 4 weeks after completion of study treatment
  • No impaired kidney function requiring dialysis
  • No uncontrolled infection
  • No HIV positivity
  • No known active hepatitis B or C

  • No cardiovascular disease including, but not limited to, any of the following:

    • Myocardial infarction within the past 6 months
    • New York Heart Association class II-IV heart failure
    • Uncontrolled angina
    • Severe uncontrolled ventricular arrhythmias
    • Clinically significant pericardial disease
    • Acute ischemic or active conduction system abnormalities by EKG
  • No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide
  • No second malignancy requiring concurrent treatment
  • No other serious medical or psychiatric illness that would preclude study compliance
  • No peripheral neuropathy ≥ grade 1

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma

    • Drugs given to prevent onset of myeloma allowed
    • Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed
  • Prior local radiotherapy with or without a brief exposure to steroids allowed

  • More than 4 weeks since prior and no concurrent radiotherapy

    • Spot radiotherapy to ≤ 3 vertebrae allowed
  • No concurrent steroids at > 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)
  • No other concurrent chemotherapy or investigational agents
  • Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate

Secondary Outcome Measures

Outcome Measure
Safety and tolerability

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: William I. Bensinger, MD, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (Anticipated)

December 1, 2008

Study Registration Dates

First Submitted

February 20, 2007

First Submitted That Met QC Criteria

February 20, 2007

First Posted (Estimate)

February 22, 2007

Study Record Updates

Last Update Posted (Estimate)

March 13, 2009

Last Update Submitted That Met QC Criteria

March 12, 2009

Last Verified

March 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000536219
  • FHCRC-2123.00

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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