A Randomized Phase III Trial of CC-5013 (Lenalidomide, NSC-703813) and Low Dose Dexamethasone (LLD) versus Bortezomib (PS-341, NSC-681239), Lenalidomide and Low Dose Dexamethasone (BLD) for Induction, in Patients with Previously Untreated Multiple Myeloma without an Intent for Immediate Autologous Stem Cell Transplant
Disease Group: Myeloma
Treatment Agent: Bortezomib
Treatment Location: Both at MDACC & Community Programs (CCOP/Network)
Estimatated Length of Stay in Houston: None
Sponsor: Southwest Oncology Group
Return Visit: Arm 1: RTC weekly for Cycle 1, every other week during cycles 2-6. Arm 2: RTC twice a week for the first 2 weeks of each cycle and then once during week 3 of each cycle. During the maintenance phase patients will RTC monthly.
Home Care: None
Primary Objective The primary objective of this study is to compare progression-free survival (PFS) in patients with newly diagnosed myeloma treated with lenalidomide plus low dose dexamethasone versus bortezomib plus lenalidomide and low dose dexamethasone. Secondary Objectives a. Assess response using the new international response criteria. b. To bank specimens for future translational medicine research. c. Follow patients to assess overall survival and other long-term outcomes stratified by intent to transplant at progression. Molecular Testing Objectives a. To evaluate custom and genome-wide single nucleotide polymorphisms in correlation with biology, prognosis and outcome for each treatment regimen. To verify the findings recently obtained with the custom BOAC SNP chip on TT2 data with respect to bone disease in the cooperative group setting. b. To use basline gene expression profiling as a tool to evaluate the biology, prognostic and risk factors, and response to therapy for both treatment regimens combined. To validate John Shaughnessy's 70 gene model developed for Total Therapy 2 (TT2) in the cooperative group setting.
IRB Review and Approval Date: 09/18/2009
Recruitment Status: Closed
Projected Accrual: 440
1) Patients must have newly diagnosed multiple myeloma (MM) with
measurable disease. Patients with non-secretory MM based upon standard
M-component criteria (i.e., measurable serum/urine M-component) are not
eligible for this study. Exception: Patients with non-secretory MM will
be eligible only if the baseline serum Freelite is elevated. (Note that
Serum Freelite must be drawn; freelite chains are not acceptable.) All
tests for establishing baseline disease status must be completed within
28 days prior to registration and documented on the Baseline and
Follow-up Tumor Assessment Form for Multiple Myeloma.
2) Patients must have received no prior chemotherapy for this disease. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration. Patients must not have received any prior treatment with bortezomib or lenalidomide.
3) Patients must be >/= 18 years of age at the time of registration.
4) Patients must have a Zubrod Performance Status (PS) of 0 - 3. (Patients with PS 3 are eligible only if it is documented by the treating physician that the patint's multiple myeloma is the central cause of his/her disability. Patients who have a PS of 3 due to other concurrent medical conditions are not eligible for this trial.)
5) Patients must have adequate marrow function as defined herein: Platelet count >/= 80 x 10^3/mcL, ANC >/= 1 x 10^3/mcL, and Hemoglobin (including patients who have been either transfused or treated with EPO) >/= 9 g/dL. All of these blood tests and bone marrow biopsy must be obtained within 28 days prior to registration.
6) Continued from Inclusion # 5: Exception: patients with biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required). In this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients.
7) Patients must be offered participation in the Myeloma Specimen Repository for banking and future research. With the patient’s consent, bone marrow aspirates and serum specimens will be submitted to the Myeloma Specimen Repository for additional testing and banking. Patient consent must be obtained before specimens may be submitted.
8) Patients must have baseline skeletal survey to include lateral skull, AP pelvis and PA chest within 28 days prior to registration.
9) Institutions must submit a local cytogenetics report and FISH analysis report obtained prior to enrollment to S0777. For FISH analysis two probes will be utilized: LSI® 13 (RBI) 13q14 SpectrumOrange™ Probe for detection of chromosome 13 deletion and LSI® p53 (17p13.1) SpectrumOrange™ Probe for detection of p53 locus on chromosome 17. If these exact probes are not available locally, it is acceptable to submit results using local protocol. This must be noted on the prestudy form. NOTE: It is not required that the results of the FISH analysis be known prior to registration, only that pre-registration specimens be drawn and sent for analysis prior to registration, and the FISH analysis report be submitted.
10) Patients with pathologic fractures, pneumonia at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis).
11) Patients must have a calculated or measured creatinine clearance > 30 cc/min. Measured creatinine clearance or serum creatinine used in calculation must be obtained within 28 days prior to registration. (CrCL=(140-patient's age x (patient's weight in kilograms) / 72 x patient's serum creatinine) (If patient is female, multiply the CrCL result by 0.85.)
12) Patients must be able to take aspirin 325 mg daily (or enoxaparin 40 mg SQ daily if patient is unable to take aspirin) as prophylactic anticoagulation. Exception: Patients receiving anticoagulation therapy such as coumadin or heparin will NOT receive aspirin, and therefore need not be able to take it.
13) Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10-14 days prior to and again within 24 hours prior to starting Cycle 1 of lenalidomide. Further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide.
14) Continued from Inclusion #13: FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a FCBP, even if they have had a successful vasectomy. A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months). All patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure.
15) All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional and federal guidelines.
16) At the time of patient registration, the treating institution's name and ID number must be provided to the Statistical Center in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base.
17) No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years.
18) Patients must be offered participation in GEP molecular studies for the evaluation of genetic polymorphisms
1) Patients must not have uncontrolled, active infection requiring
intravenous antibiotics, New York Heart Association (NYHA) Class III or
Class IV heart failure, myocardial infarction within the last 6 months,
history of treatment for clinically significant ventricular cardiac
arrhythmias, poorly controlled hypertension, or poorly controlled
diabetes mellitus. Patients must have undergone an EKG within 28 days
prior to registration.
2) Patients must not have any psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
3) Patients must not be Hepatitis B, Hepatitis C or HIV positive as these conditions could interfere with endpoint assessment. Patients must have a negative Hepatitis B, Hepatits C and HIV test performed within 28 days prior to registration. Exception: Treatment-sensitive HIV infection patients will be eligible provided that immunological and virologic indices are indicative of favorable long-term survival prospects on the basis of HIV infection, but whose life expectancy is limited predominantly by multiple myeloma rather than HIV infection in the judgment of the treating physician.
4) Patients must not have a history of cerebral vascular accident with persistent neurologic deficits
5) No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for five years.