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

Multiple Myeloma Clinical Trial

Official title:

S0417 A Phase II Study of Bortezomib (Velcade™, PS-341), Thalidomide, and Dexamethasone in Patients With Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00124579
• Other study ID #: S0417
• Secondary ID: S0417U10CA032102
• Status: Terminated
• Phase: Phase 2
• Start date: August 2005
• Est. completion date: June 2010

Study information

• Verified date: July 2018
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 2010
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• 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

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• bortezomib
induction: 1 mg/m2 IV push days 1, 4, 8, 11 every 21 days
• 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
• thalidomide
100 mg/d PO days 1-21 every 21 days

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	American Fork Hospital	American Fork	Utah
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	Billings Clinic Cancer Center	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Center for Cancer Medicine and Blood Disorders, PA	El Paso	Texas
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Metro Health Hospital	Grand Rapids	Michigan
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Regional Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Holland Community Hospital	Holland	Michigan
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio
United States	Foote Hospital	Jackson	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Logan Regional Hospital	Logan	Utah
United States	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Hackley Hospital	Muskegon	Michigan
United States	Hematology Oncology Consultants - Naperville	Naperville	Illinois
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Latter Day Saints Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Wesley Medical Center	Wichita	Kansas
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Tod Children's Hospital	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate Complete Remission (CR), Remission (R), and Partial Remission (PR).	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.	1 year
Secondary	Toxicity Evaluation	To evaluate the qualitative and quantitative toxicities associated with this regimen.	From date of protocol therapy start to date of protocol therapy end, i.e., up to about 3.5 years
Secondary	Progression-Free Survival	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	about 12-18 months