S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
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| ClinicalTrials.gov Identifier: NCT00124579 |
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Recruitment Status :
Terminated
(poor accrual)
First Posted : July 28, 2005
Results First Posted : April 19, 2013
Last Update Posted : August 9, 2018
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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 |
OBJECTIVES:
- 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 |
| Allocation: | N/A |
| 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 |
|---|---|
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Experimental: bortezomib with thalidomide and dexamethasone
bortezomib with thalidomide and dexamethasone
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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 |
- 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.
- Toxicity Evaluation [ Time Frame: From date of protocol therapy start to date of protocol therapy end, i.e., up to about 3.5 years ]To evaluate the qualitative and quantitative toxicities associated with this regimen.
- Progression-Free Survival [ Time Frame: about 12-18 months ]From date of initial registration to date of progression/relapse of disease (> 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc.) or death from any cause, whichever came first, up to 5 years
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| Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Diagnosis of multiple myeloma (MM)
- Active disease
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Relapsed or refractory disease after ≥ 1 prior therapy for MM, that may have included autologous or allogeneic stem cell transplantation
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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
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- Measurable disease
- No evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of M-protein, and skin changes) syndrome
- Must be registered on protocol SWOG-S0334
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-2 (unless due to bone pain)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 50,000/mm^3
Hepatic
- AST or ALT ≤ 3 times upper limit of normal (ULN)
- Bilirubin ≤ 3 times ULN
Renal
- Creatinine clearance > 30 mL/min
Cardiovascular
- No New York Heart Association class III or IV congestive heart failure
- No myocardial infarction within the past 6 months
- No poorly controlled hypertension
Other
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- At least 14 days since prior chemotherapy (28 days for nitrosoureas) and recovered
Endocrine therapy
- Not specified
Radiotherapy
- At least 14 days since prior radiotherapy and recovered
Surgery
- Not specified
Other
- No prior bortezomib alone or combined with thalidomide
- Concurrent participation on protocol SWOG-S0309 allowed
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 ClinicalTrials.gov identifier (NCT number): NCT00124579
Show 127 study locations
| Principal Investigator: | Gordan Srkalovic, MD, PhD | Sparrow Regional Cancer Center | |
| Principal Investigator: | Mohamad A. Hussein, MD | The Cleveland Clinic |
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00124579 |
| 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: | August 9, 2018 |
| Last Verified: | July 2018 |
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stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma refractory multiple myeloma |
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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 Thalidomide |
Dexamethasone Bortezomib Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunosuppressive Agents Immunologic Factors |