Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Dexamethasone With or Without Thalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI	E-E1A00 NCT00033332, E1A00

Objectives

1. Compare the response rate of patients with newly diagnosed multiple myeloma treated with dexamethasone with or without thalidomide.
2. Compare the toxicity of these regimens in these patients.
3. 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.

Entry 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

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)

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm³
• Platelet count greater than 50,000/mm³
• 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

Expected Enrollment

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

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.

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.

Rajkumar SV, Blood E, Vesole D, et al.: 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 24 (3): 431-6, 2006.[PUBMED Abstract]

Rajkumar SV, Blood E, Vesole DH, et al.: A randomised phase III trial of thalidomide plus dexamethasone versus dexamethasone in newly diagnosed multiple myeloma (E1A00): a trial coordinated by the Eastern Cooperative Oncology Group. [Abstract] J Clin Oncol 22 (Suppl 14): A-6508, 560s, 2004.

Rajkumar SV, Blood E, Vesole DH, et al.: Thalidomide plus dexamethasone versus dexamethasone alone in newly diagnosed multiple myeloma (E1A00): results of a phase III trial coordinated by the Eastern Cooperative Oncology Group. [Abstract] Blood 104 (11): A-205, 2004.

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 1 (3): 188-9, 2003.[PUBMED Abstract]

Ballester O: The emperor's new clothes or the current practice of clinical trials for multiple myeloma in the USA. Cancer Invest 26 (5): 445-7, 2008.[PUBMED Abstract]

Johnson DC, Corthals S, Ramos C, et al.: Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping. Blood 112 (13): 4924-34, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

S. Rajkumar, MD, Protocol chair		Ph: 507-284-8430 Email: rajks@mayo.edu

Registry Information
Official Title		A Randomized Phase III Trial Of Thalidomide (NSC # 66847) Plus Dexamethasone Versus Dexamethasone In Newly Diagnosed Multiple Myeloma
Trial Start Date		2002-04-17
Registered in ClinicalTrials.gov		NCT00033332
Date Submitted to PDQ		2002-02-07
Information Last Verified		2005-11-30
NCI Grant/Contract Number		CA21115