Clinical Trials

Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma

Location:

Scottsdale and Phoenix,  AZ,  Rochester,  MN

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES:

Primary

- To compare progression-free survival of patients with newly diagnosed multiple myeloma treated with lenalidomide and low-dose dexamethasone with or without bortezomib.

Secondary

- To assess response using the new international response criteria.

- To bank specimens for future research.

- To assess overall survival and other long-term outcomes stratified by intent to undergo transplantation at progression.

- To verify the reported benefit of bortezomib in promoting bone repair/healing by comparing and contrasting the bone healing as determined by achievement of MRI-CR (closed as of 10/15/10).

- To utilize MRI for accurate baseline staging plus evaluation of response and progression (closed as of 10/15/10).

- To compare achievement of MRI-CR with achievement of x-ray-CR (closed as of 10/15/10).

- To evaluate custom and genome-wide single nucleotide polymorphisms (SNPs) in correlation with biology, prognosis and outcome for both treatment regimens combined.

- 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.

- To use baseline 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 risk model developed for Total Therapy 2 (TT2) in the cooperative group setting.

OUTLINE: Patients are stratified according to the International Staging System (I vs II vs III) and intent to undergo transplantation at relapse (yes vs no).

- Induction therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral dexamethasone once daily on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive oral dexamethasone once daily on days 1, 2, 4, 5, 8, 9, 11, and 12; oral lenalidomide once daily on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

In both arms, patients who intend to undergo transplantation at relapse undergo peripheral blood stem cell collection, preferably after course 2.

- Maintenance therapy: After the completion of at least 4 courses (arm I) or at least 6 courses (arm II) of induction therapy, patients receive maintenance therapy comprising oral dexamethasone once daily on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow biopsy at baseline and periodically during study for correlative studies. Patients may also undergo blood sample collection.

After completion of study treatment, patients are followed periodically for up to 6 years.

Who is eligible to participate?

DISEASE CHARACTERISTICS:

- Newly diagnosed multiple myeloma (MM)

- Stage I, II, or III disease by the New International Staging System

- Measurable disease

- Nonsecretory MM based upon standard M-component criteria (i.e., measurable serum/urine M-component) is not allowed unless the baseline serum free light chain level (Freelite?) is elevated

- Serum Freelite must be drawn

- No freelite chains

- Must be offered participation in the Myeloma Specimen Repository for banking and future research, and in the Gene Expression Profiling (GEP) molecular studies for the evaluation of genetic polymorphisms

- Must have baseline skeletal survey, including lateral skull, anteroposterior (AP) pelvis and posteroanterior (PA) chest within 28 days prior to study entry

- Institutions must submit a local cytogenetics report and FISH analysis prior to study entry

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-3

- Platelet count ≥ 80,000/mm³*

- ANC ≥ 1,000/mm³*

- Hemoglobin ≥ 9.0 g/dL* (including patients who have been transfused or treated with epoetin)

- Creatinine clearance > 30 cc/min

- FEV_1 and FVC ≥ 50% of predicted**

- DLCO ≥ 50% of predicted**

- No uncontrolled, active infection requiring IV antibiotics

- No NYHA class III-IV heart failure

- No myocardial infarction within the past 6 months

- No history of treatment for clinically significant ventricular cardiac arrhythmias

- No poorly controlled hypertension

- No poorly controlled diabetes mellitus

- No chronic obstructive or chronic restrictive pulmonary disease

- Must have undergone an EKG within the past month

- No psychiatric illness that could potentially interfere with the completion of study treatment

- No history of cerebral vascular accident with persistent neurologic deficits

- No other prior malignancy except 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 5 years

- No hepatitis B or C positivity

- HIV negative***

- 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

- Patients with pathologic fractures, pneumonia at diagnosis, or symptomatic hyperviscosity syndrome must have these conditions attended to prior to study entry (i.e., intramedullary rod, IV antibiotics, or plasmapheresis)

- Patients must have baseline skeletal survey that include lateral skull, anteroposterior (AP) pelvis, and posteroanterior (PA) chest within the past 28 days NOTE: *Except patients with biopsy-proven heavy-marrow involvement, defined as having ≥ 30% marrow cellularity with > 50% of the cells being malignant plasma cells (documented marrow results required)

NOTE: **Patients who are unable to complete pulmonary function tests due to bone pain or fracture must undergo high resolution CT scan of the chest and have acceptable arterial blood gases, defined as P02 > 70; these tests must be completed within 42 days prior to study entry

NOTE: ***Patients with treatment-sensitive HIV infection are eligible provided 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 judgement of the treating physician

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for this disease

- No prior radiotherapy to a large area of the pelvis (i.e., more than half of the pelvis)

- No prior bortezomib or lenalidomide

- Prior steroid treatment allowed provided treatment was no more than 2 weeks in duration

- Must be able to take concurrent aspirin 325 mg daily (or enoxaparin 40 mg subcutaneously daily if allergic to aspirin) as prophylactic coagulation

Last updated: 03/26/2012

NCT ID:

NCT00644228