Clinical trial NCT00033332: Dexamethasone With or Without Thalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
Official title: A Randomized Phase III Trial Of Thalidomide (NSC # 66847) Plus Dexamethasone Versus Dexamethasone In Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining dexamethasone and thalidomide may kill more cancer cells. It is not yet known whether dexamethasone is more effective with or without thalidomide in treating multiple myeloma.

PURPOSE: Randomized phase III trial to determine the effectiveness of dexamethasone with or without thalidomide in treating patients who have multiple myeloma.

Detailed description: OBJECTIVES:

* Compare the response rate of patients with newly diagnosed multiple myeloma treated with dexamethasone with or without thalidomide.
* Compare the toxicity of these regimens in these patients.
* Assess the effect of thalidomide on bone marrow microvessel density and angiogenesis grade and on the expression of vascular endothelial growth factor and basic fibroblast growth factor in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral thalidomide once daily on days 1-28 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients also receive either pamidronate IV over 2-4 hours or zoledronate IV over 15 minutes on day 1 for bone strengthening.
* Arm II: Patients receive dexamethasone and pamidronate or zoledronate as in arm I.

Treatment in both arms repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional courses after the fourth course at the physician's discretion.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 194 patients (97 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Newly diagnosed symptomatic multiple myeloma confirmed by the following:

  * Bone marrow plasmacytosis with at least 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytosis
  * Monoclonal protein (M protein) at least 1.0 g/dL on serum protein electrophoresis or at least 200 mg of monoclonal light chain on a 24-hour urine protein electrophoresis
* No smoldering myeloma or monoclonal gammopathy of undetermined significance

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1,000/mm\^3
* Platelet count greater than 50,000/mm\^3
* Hemoglobin greater than 7 g/dL

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* ALT and AST no greater than 2.5 times upper limit of normal

Renal:

* Creatinine less than 3 mg/dL

Cardiovascular:

* No prior or concurrent deep venous thrombosis

Other:

* Prior malignancy allowed provided the following criteria are met:

  * Received prior treatment with curative intent
  * Free of disease for the time period appropriate for cure of the specific cancer
* No grade 2 or greater peripheral neuropathy due to other medical conditions
* No active infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use 1 highly effective method and 1 additional method of contraception for 1 month before, during, and for 4 weeks after study for women and effective barrier contraception for men during and for 4 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior biologic therapy for multiple myeloma
* No other concurrent biologic therapy for multiple myeloma

Chemotherapy:

* No prior chemotherapy for multiple myeloma
* No other concurrent chemotherapy for multiple myeloma

Endocrine therapy:

* More than 6 months since prior systemic dexamethasone or glucocorticoids
* No concurrent corticosteroids

Radiotherapy:

* At least 4 weeks since prior palliative, localized radiotherapy
* Concurrent palliative, localized radiotherapy allowed at the physician's discretion

Surgery:

* Not specified

Other:

* No prior systemic therapy for multiple myeloma, except bisphosphonates
* No concurrent anticoagulant therapy for deep vein thrombosis
* No concurrent barbiturates or alcohol (thalidomide arm)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Inc.
state: Colorado
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: MBCCOP - Howard University Cancer Center
state: District of Columbia
city: Gainesville
country: United States
facility: Veterans Affairs Medical Center - Gainesville
state: Florida
city: Gainesville
country: United States
facility: UF Shands Cancer Center
state: Florida
city: Miami
country: United States
facility: Veterans Affairs Medical Center - Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tuft-New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Veterans Affairs Medical Center - Omaha
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: Bronx
country: United States
facility: MBCCOP-Our Lady of Mercy Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Tulsa
country: United States
facility: CCOP - Oklahoma
state: Oklahoma
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Affairs Medical Center - Pittsburgh
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
city: San Juan
country: Puerto Rico
facility: Veterans Affairs Medical Center - San Juan
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospitals
Study officials:
affiliation: Mayo Clinic
name: S. V. Rajkumar, MD
role: STUDY_CHAIR
References:
citation: Ballester O. The emperor's new clothes or the current practice of clinical trials for multiple myeloma in the USA. Cancer Invest. 2008 Jun;26(5):445-7. doi: 10.1080/07357900701874641.
citation: Johnson DC, Corthals S, Ramos C, Hoering A, Cocks K, Dickens NJ, Haessler J, Goldschmidt H, Child JA, Bell SE, Jackson G, Baris D, Rajkumar SV, Davies FE, Durie BG, Crowley J, Sonneveld P, Van Ness B, Morgan GJ. Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping. Blood. 2008 Dec 15;112(13):4924-34. doi: 10.1182/blood-2008-02-140434. Epub 2008 Sep 19.
citation: Kumar S, Greipp PR, Haug JL, et al.: Correlation of bone marrow angiogenesis and response to thalidomide dexamethasone in multiple myeloma. [Abstract] J Clin Oncol 24 (Suppl 18): A-7621, 451s, 2006.
citation: Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. doi: 10.1200/JCO.2005.03.0221. Epub 2005 Dec 19.
citation: Greipp PR. Eastern Cooperative Oncology Group E1A00: phase III randomized study of dexamethasone with or without thalidomide in patients with newly diagnosed multiple myeloma. Clin Adv Hematol Oncol. 2003 Mar;1(3):188-9. No abstract available.