Clinical trial NCT00124579: S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official title: S0417 A Phase II Study of Bortezomib (Velcade™, PS-341), Thalidomide, and Dexamethasone in Patients With Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-07-28
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate Complete Remission (CR), Remission (R), and Partial Remission (PR).
timeFrame: 1 year
Secondary outcomes:
measure: Toxicity Evaluation
timeFrame: From date of protocol therapy start to date of protocol therapy end, i.e., up to about 3.5 years
measure: Progression-Free Survival
timeFrame: about 12-18 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Naperville
country: United States
facility: Hematology Oncology Consultants - Naperville
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: Davenport
country: United States
facility: Genesis Regional Cancer Center at Genesis Medical Center
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center - West Campus
state: Iowa
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital - Butterworth Campus
state: Michigan
city: Grand Rapids
country: United States
facility: Metro Health Hospital
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Jackson
country: United States
facility: Foote Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Cape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Regional Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Middletown
country: United States
facility: Tucker Center for Cancer Care at Orange Regional Medical Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group at Cleveland Clinic Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Wright-Patterson Air Force Base
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Youngstown
country: United States
facility: Tod Children's Hospital
state: Ohio
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center & Children's Hospital
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: El Paso
country: United States
facility: Center for Cancer Medicine and Blood Disorders, PA
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Houston
country: United States
facility: St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
state: Texas
city: Houston
country: United States
facility: Veterans Affairs Medical Center - Houston
state: Texas
city: Lackland Air Force Base
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Cedar City
country: United States
facility: Sandra L. Maxwell Cancer Center
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Sedro-Woolley
country: United States
facility: North Puget Oncology at United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Sparrow Regional Cancer Center
name: Gordan Srkalovic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Mohamad A. Hussein, MD
role: PRINCIPAL_INVESTIGATOR
References: