Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients With Previously Untreated Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients With Previously Untreated Multiple Myeloma
OBJECTIVES:
- Compare the progression-free survival of patients with previously untreated stage I,
II, or III multiple myeloma treated with dexamethasone with or without lenalidomide.
- Compare the overall response rate in patients treated with these regimens.
- Compare the major response rate (indicated by greater than 75% decrease in M-protein)
in patients treated with these regimens.
- Compare the overall survival and time to best response in patients treated with these
regimens.
- Compare the toxicity profile of these regimens, including thrombotic complications, in
these patients.
- Compare the effect of these regimens on gene expression and proteomic analysis in these
patients.
OUTLINE: This is a randomized, double-blind, crossover, multicenter study. Patients are
stratified according to disease stage by the International Staging System (I vs II vs III)
and Zubrod performance status (0-1 vs 2-3). Patients are randomized to 1 of 2 treatment
arms.
Arm I
- Induction therapy: Patients receive oral dexamethasone (DM) on days 1-4, 9-12, and
17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3
courses in the absence of disease progression or unacceptable toxicity.
- Maintenance therapy: Patients receive oral DM on days 1-4 and 15-18 and oral
lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Arm II
- Induction therapy: Patients receive DM as in arm I induction and oral placebo on days
1-28. Treatment repeats as in arm I induction.
Patients with responding or stable disease proceed to maintenance therapy. Patients with
disease progression during induction therapy cross over and receive unblinded treatment with
DM and lenalidomide as in arm I induction. Patients with responding or stable disease after
unblinded induction therapy receive unblinded maintenance therapy with DM and lenalidomide
as in arm I maintenance.
- Maintenance therapy: Patients receive oral DM as in arm I maintenance and oral placebo
on days 1-21. Courses repeat as in arm I maintenance.
Patients with disease progression during maintenance therapy cross over and receive
unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding
or stable disease after unblinded induction therapy proceed to unblinded maintenance therapy
with DM and lenalidomide as in arm I maintenance.
Patients are followed periodically for up to 5 years.
PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this
study within 4 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Previously untreated multiple myeloma
- Stage I, II, or III disease by the International Staging System
- Measurable M-protein as defined by 1 of the following:
- Serum M-protein at least 1.0 g/dL by serum protein electrophoresis or
immunoelectrophoresis
- Urinary M-protein excretion at least 200 mg/24 hours
- No nonsecretory multiple myeloma
- Not planning to undergo future autologous stem cell transplantation
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-3* NOTE: *Zubrod 3 allowed only if multiple myeloma is the central cause of
disability
Life expectancy
- Not specified
Hematopoietic
- Platelet count at least 80,000/mm^3*
- Absolute neutrophil count at least 1,000/mm^3*
- Hemoglobin at least 9 g/dL* (epoetin alfa or transfusion allowed) NOTE: *Unless due
to greater than 50% marrow involvement by myeloma on biopsy
Hepatic
- AST/ALT no greater than 3 times upper limit of normal* NOTE: *Values outside of this
range are allowed at the investigator's discretion
Renal
- Creatinine no greater than 2.5 mg/dL* NOTE: *Values outside of this range are allowed
at the investigator's discretion
Cardiovascular
- No New York Heart Association class III or IV heart failure
- No myocardial infarction within the past 6 months
- No poorly controlled hypertension
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 4 weeks before, during, and for
4 weeks after study treatment
- Female patients must use 2 reliable forms of contraception simultaneously
- Male patients must use effective barrier contraception
- No uncontrolled active infection requiring IV antibiotics
- No poorly controlled diabetes mellitus that would preclude ability to take oral
glucocorticoids
- No other serious medical condition that would preclude study participation
- No psychiatric illness that would preclude study participation
- 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
- Must be able to take aspirin by mouth at a dose of 325 mg per day or enoxaparin
subcutaneously at a dose of 40 mg per day as a form of thrombotic prophylaxis, except
if already on therapeutic anticoagulant medication
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior interferon or thalidomide
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Prior high-dose dexamethasone allowed provided duration of administration was no more
than 4 days
Radiotherapy
- Prior localized radiotherapy allowed provided it was not to the sole site of
evaluable disease
Surgery
- Not specified
Other
- No prior treatment for clinically significant ventricular cardiac arrhythmias
- Concurrent bisphosphonates allowed
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Progression-free survival
Safety Issue:
No
Principal Investigator
Jeffrey A. Zonder, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000306449
NCT ID:
NCT00064038
Start Date:
November 2004
Completion Date:
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| William Beaumont Hospital - Royal Oak Campus | Royal Oak, Michigan 48073 |
| Utah Cancer Specialists at UCS Cancer Center | Salt Lake City, Utah 84106 |
