Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase III trial is studying giving lenalidomide and dexamethasone together with bortezomib to see how well it works compared to dexamethasone and lenalidomide alone in treating patients with previously untreated multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. It is not yet known whether lenalidomide and dexamethasone is more effective with or without bortezomib in treating multiple myeloma

Further Study Information

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To assess response using the new international response criteria. II. To bank specimens for future research. III. To assess overall survival and other long-term outcomes stratified by intent to undergo transplantation at progression.

IV. 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).

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

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

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

VIII. 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.

IX. 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.

X. 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.

Eligibility Criteria

Inclusion Criteria:

• 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

• 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

• 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Brian G. Durie

Principal Investigator

U.S.A.
Texas
	San Antonio
	Southwest Oncology Group
		Brian G. M Durie	Ph: 734-998-7191

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00644228
Information obtained from ClinicalTrials.gov on January 14, 2013

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