Official Title: “An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) Versus Melphalan, Prednisone and Lenalidomide (Revlimid™) (MPR) in Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy”

RATIONALE: Drugs used in chemotherapy, such as melphalan and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It is not yet known whether melphalan and prednisone are more effective when given together with thalidomide or lenalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying giving melphalan and prednisone together with thalidomide to see how well it works compared with giving melphalan and prednisone together with lenalidomide in treating patients with newly diagnosed multiple myeloma.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

Study Primary Completion Date: August 2009

OBJECTIVES:

Primary - To compare progression-free survival between patients receiving melphalan, prednisone, and thalidomide versus melphalan, prednisone, and lenalidomide in newly diagnosed multiple myeloma patients who are not candidates for high-dose therapy.

Secondary - To compare overall survival between both arms. - To compare response rates and depth of response in these patients. - To compare the incidence of toxicities in these patients. - To validate the TC classification of myeloma as a prognostic tool using gene expression profiling at diagnosis.

Tertiary - To compare quality-of-life (QOL) change between arms based on the FACT-Ntx TOI from baseline to the end of course 24 (maintenance therapy). - To examine the impact of differential treatment responses on QOL based on the FACT-Ntx TOI up to course 38. - To obtain prospective data on myeloma specific QOL attributes.

OUTLINE: This is a multicenter study. Patients are stratified according to ISS stage (I-II vs III) and age (< 65 vs ≥ 65). Patients are randomized to 1 of 2 treatment arms. - Arm I: - Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. - Maintenance therapy: Patients receive oral thalidomide once daily and continue in the absence of disease progression. - Arm II: - Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. - Maintenance therapy: Patients receive oral lenalidomide once daily on days 1-21.

Treatment repeats every 28 days in the absence of disease progression.

Quality of life is assessed at baseline and periodically during treatment.

Peripheral blood and bone marrow samples are collected at baseline for gene expression profiling analysis.

After completion of study treatment, patients will be followed periodically for 10 years.

Intervention(s) in this Clinical Trial

• Drug: lenalidomide
  • Oral
• Drug: melphalan
  • Oral
• Drug: prednisone
  • Oral
• Drug: thalidomide
  • Oral

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Arm I
  • Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral thalidomide once daily and continue in the absence of disease progression.
• Experimental: Arm II
  • Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression.

Primary Measures

• Progression-free survival
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No

Secondary Measures

• Response rates and depth of response comparison
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes
• Quality-of-life (QOL) change comparison of arms measured by FACT-Ntx TOI from baseline to course 24
  • Safety Issue?: No
• Differential treatment response on QOL measured by FACT-Ntx TOI from baseline to course 38
  • Safety Issue?: No
• TC classification validation of myeloma as a prognostic tool using gene expression profiling
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma (MM), meeting the following criteria:
• Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
• Symptomatic disease with evidence of end-organ damage at initial diagnosis that prompted the initiation of therapy, including ≥ 1 of the following:
• Anemia
• Hypercalcemia
• Bone disease (lytic bone lesions or pathologic fracture)
• Renal dysfunction
• No smoldering MM, defined by all of the following:
• Serum monoclonal protein ≥ 3 g/dL
• Bone marrow plasma cells ≥ 10% or greater
• Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction
• No monoclonal gammopathy of undetermined significance, defined by all of the following:
• Serum monoclonal protein < 3 g/dL
• Bone marrow plasma cells ≤ 10%
• Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction
• Previously untreated for MM
• Patients 18 to 64 years old must not be a candidate for autologous stem cell transplantation or have declined transplantation or other alternative treatment

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Hemoglobin > 7 g/dL
• Platelet count > 75,000/mm³
• ANC > 1,000/mm³
• Creatinine < 2.5 mg/dL
• Direct bilirubin ≤ 1.5 mg/dL
• ALT and AST ≤ 2.5 times upper limit of normal
• No uncontrolled intercurrent illness that would limit compliance with the study including, but not limited to, any of the following:
• Uncontrolled hypertension
• Symptomatic congestive heart failure
• Unstable angina
• Uncontrolled cardiac arrhythmia
• Uncontrolled psychiatric illness or social situation
• Prior history of Stevens Johnson syndrome
• No peripheral neuropathy ≥ grade 2
• No active uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception 4 weeks prior to, during, and 4 weeks after completion of study treatment
• Must be able to take prophylatic aspirin 325mg/day or low-molecular weight heparin or coumadin
• No second active malignancy requiring treatment within the past 2 years, except for basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior treatment for myeloma except for either of the following:
• Prednisone or dexamethasone treatment for myeloma for a duration of less than 4 weeks
• Prednisone or dexamethasone in combination with thalidomide or lenalidomide for a duration of less than 2 weeks total
• Concurrent bisphosphonates or growth factors (i.e., erythropoietin) for MM allowed
• Concurrent localized radiation therapy is allowed for pain control at the physician's discretion

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eastern Cooperative Oncology Group

Overall Clinical Trial Officials and Contacts

A. Keith Stewart, MD Study Chair Mayo Clinic Scottsdale  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00602641

Study ID Number: CDR0000583984

ClinicalTrials.gov Identifier: NCT00602641

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database