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

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
cyclophosphamide
dexamethasone
thalidomide
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alta Bates Summit Comprehensive Cancer Center
  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
  • Desert Regional Medical Center Comprehensive Cancer Center
  • Sutter Cancer Center
  • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
  • St. Vincent's Comprehensive Cancer Center - Manhattan
  • Oregon Health and Science University Cancer Institute
  • Lone Star Oncology - Austin
  • Seattle Cancer Care Alliance
  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Response rate

Secondary Outcome Measures

Safety and tolerability

Full Information

First Posted
February 20, 2007
Last Updated
March 12, 2009
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00438841
Brief Title
Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma
Official Title
A Phase II Trial With VELCADE® (PS-341), Cytoxan (Cyclophosphamide), Dexamethasone and Thalomid® (VEL-CTD) in Previously Untreated Multiple Myeloma Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2009
Overall Recruitment Status
Unknown status
Study Start Date
August 2006 (undefined)
Primary Completion Date
December 2008 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
thalidomide
Primary Outcome Measure Information:
Title
Response rate
Secondary Outcome Measure Information:
Title
Safety and tolerability

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William I. Bensinger, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alta Bates Summit Comprehensive Cancer Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Desert Regional Medical Center Comprehensive Cancer Center
City
Palm Springs
State/Province
California
ZIP/Postal Code
92262
Country
United States
Facility Name
Sutter Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
St. Vincent's Comprehensive Cancer Center - Manhattan
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Oregon Health and Science University Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Lone Star Oncology - Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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