S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00124579
Recruitment Status : Terminated (poor accrual)
First Posted : July 28, 2005
Results First Posted : April 19, 2013
Last Update Posted : March 25, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Brief Summary:

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

PURPOSE: This phase II trial is studying how well giving bortezomib together with thalidomide and dexamethasone works in treating patients with relapsed or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: bortezomib Drug: dexamethasone Drug: thalidomide Phase 2

Detailed Description:


  • Determine the confirmed overall response rate (complete remission, remission, and partial remission) in patients with relapsed or refractory multiple myeloma treated with bortezomib, thalidomide, and dexamethasone.
  • Determine overall and progression-free survival of patients treated with this regimen.
  • Determine the qualitative and quantitative toxic effects of this regimen in these patients.
  • Correlate, preliminarily, treatment with bortezomib with the activation of osteoblasts in these patients.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11, oral thalidomide once daily on days 1-21, and oral dexamethasone once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days until achievement of confirmed complete remission (CR), remission (R), or partial remission (PR) OR for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving confirmed CR, R, or PR who reach a plateau prior to receiving the maximum 8 courses of induction therapy OR who achieve confirmed CR, R, or PR after receiving the maximum 8 courses of induction therapy proceed to maintenance therapy. Patients achieving stable disease after receiving the maximum 8 courses of induction therapy either proceed to maintenance therapy or receive further treatment with bortezomib, thalidomide, and dexamethasone off-study.

  • Maintenance therapy: Patients receive oral dexamethasone on days 1-4. Courses repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed within 30 days and then every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: S0417 A Phase II Study of Bortezomib (Velcade™, PS-341), Thalidomide, and Dexamethasone in Patients With Refractory Multiple Myeloma
Study Start Date : August 2005
Actual Primary Completion Date : June 2008
Actual Study Completion Date : June 2010

Arm Intervention/treatment
Experimental: bortezomib with thalidomide and dexamethasone
bortezomib with thalidomide and dexamethasone
Drug: bortezomib
induction: 1 mg/m2 IV push days 1, 4, 8, 11 every 21 days
Drug: dexamethasone
induction: 20 mg/d PO days 1, 2, 4, 5, 8, 9, 11, 12 every 21 days maintenance: 40 mg days 1-4 every 28 days until progression
Drug: thalidomide
100 mg/d PO days 1-21 every 21 days

Primary Outcome Measures :
  1. Overall Response Rate Complete Remission (CR), Remission (R), and Partial Remission (PR). [ Time Frame: 1 year ]

    Responses are defined as follows:

    Complete Remission: Absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-proteins on immunofixation electrophoresis studies. Normalization of serum concentrations of normal immunoglobulins is not required for CR. There must also be no evidence of increasing anemia. Bone marrow cellularity must be ≥ 20% with plasma cells ≤ 5%.

    Remission: A ≥ 75% reduction in the serum M-protein, and if a urine M-protein (Bence-Jones protein) is present, either a ≥ 90% reduction in this protein, or a urine M-protein < 0.2gm/day. Bone marrow plasma cells must be ≤ 5%.

    Partial Remission: A ≥ 50% reduction in the serum M-protein, and if present, a ≥ 50% reduction in the urine M-protein (Bence-Jones protein). Bone marrow plasma cells must not be increased from baseline level.

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: From date of protocol therapy start to date of protocol therapy end. ]
    To evaluate the qualitative and quantitative toxicities associated with this regimen.

  2. Progression-Free Survival [ Time Frame: about 12-18 months ]
    From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of multiple myeloma (MM)

    • Active disease
  • Relapsed or refractory disease after ≥ 1 prior therapy for MM, that may have included autologous or allogeneic stem cell transplantation

    • Relapse is defined as the occurrence of any of the following during or after prior treatment:

      • Myeloma protein level increase by > 100% from the lowest previously recorded level
      • Myeloma protein level increase above the defined response criteria for partial remission
      • Reappearance of any myeloma peak that had disappeared during the prior treatment
      • Increase in the size and number of lytic bone lesions and/or focal lesions by x-ray, MRI, positron emission tomography, and/or CT scan
    • Refractory disease is defined as no response (i.e., not achieving complete remission, remission, or partial remission) to prior therapy
  • Measurable disease
  • No evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of M-protein, and skin changes) syndrome
  • Must be registered on protocol SWOG-S0334



  • 18 and over

Performance status

  • Zubrod 0-2 (unless due to bone pain)

Life expectancy

  • Not specified


  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 50,000/mm^3


  • AST or ALT ≤ 3 times upper limit of normal (ULN)
  • Bilirubin ≤ 3 times ULN


  • Creatinine clearance > 30 mL/min


  • No New York Heart Association class III or IV congestive heart failure
  • No myocardial infarction within the past 6 months
  • No poorly controlled hypertension


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use effective double method contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study treatment (during and for 4 weeks after completion of study treatment for male patients)
  • No blood, ova, or sperm donation during study treatment
  • No active infection requiring antibiotics
  • No neurotoxicity ≥ grade 2
  • No diabetes mellitus
  • No other serious medical or psychiatric illness that would preclude study treatment
  • No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix


Biologic therapy

  • See Disease Characteristics


  • At least 14 days since prior chemotherapy (28 days for nitrosoureas) and recovered

Endocrine therapy

  • Not specified


  • At least 14 days since prior radiotherapy and recovered


  • Not specified


  • No prior bortezomib alone or combined with thalidomide
  • Concurrent participation on protocol SWOG-S0309 allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00124579

  Show 127 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Gordan Srkalovic, MD, PhD Sparrow Regional Cancer Center
Principal Investigator: Mohamad A. Hussein, MD The Cleveland Clinic

Responsible Party: Southwest Oncology Group Identifier: NCT00124579     History of Changes
Other Study ID Numbers: S0417
S0417 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: July 28, 2005    Key Record Dates
Results First Posted: April 19, 2013
Last Update Posted: March 25, 2015
Last Verified: March 2015

Keywords provided by Southwest Oncology Group:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents