Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

Condition(s) targeted: Multiple Myeloma and Plasma Cell Neoplasm

Intervention: lenalidomide (Drug); melphalan (Drug); prednisone (Drug); thalidomide (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Eastern Cooperative Oncology Group

Official(s) and/or principal investigator(s):
A. Keith Stewart, MD, Study Chair, Affiliation: Mayo Clinic Scottsdale
S. V. Rajkumar, MD, Affiliation: Mayo Clinic

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.

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

Study design: Treatment, Randomized, Active Control

Primary outcome:

Progression-free survival

Overall survival

Secondary outcome:

Response rates and depth of response comparison

Toxicity

Quality-of-life (QOL) change comparison of arms measured by FACT-Ntx TOI from baseline to course 24

Differential treatment response on QOL measured by FACT-Ntx TOI from baseline to course 38

TC classification validation of myeloma as a prognostic tool using gene expression profiling

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Kaiser Permanente Medical Office -Vandever Medical Office, San Diego, California 92120, United States; Recruiting
Han A. Koh, Phone: 619-528-2596

Front Range Cancer Specialists, Fort Collins, Colorado 80528, United States; Recruiting
Robert F. Marschke, Jr., Phone: 970-212-7600

Poudre Valley Hospital, Fort Collins, Colorado 80524, United States; Recruiting
Clinical Trials Office - Poudre Valley Hospital, Phone: 970-495-8226

McCreery Cancer Center at Ottumwa Regional, Ottumwa, Iowa 52501, United States; Recruiting
Robert J. Behrens, Phone: 641-684-2946

Mercy Cancer Center at Mercy Medical Center - North Iowa, Mason City, Iowa 50401, United States; Recruiting
Clinical Trials Office - Mercy Cancer Center at Mercy Medical, Phone: 641-422-6304

Lawrence Memorial Hospital, Lawrence, Kansas 66044, United States; Recruiting
Shaker R. Dakhil, MD, FACP, Phone: 316-262-4467

Wesley Medical Center, Wichita, Kansas 67214, United States; Recruiting
Shaker R. Dakhil, MD, FACP, Phone: 316-262-4467

CCOP - Duluth, Duluth, Minnesota 55805, United States; Recruiting
Daniel Nikcevich, MD, PhD, Phone: 218-786-3625

Duluth Clinic Cancer Center - Duluth, Duluth, Minnesota 55805-1983, United States; Recruiting
Clinical Trials Office - Duluth Clinic Cancer Center - Duluth, Phone: 218-786-3308

Miller - Dwan Medical Center, Duluth, Minnesota 55805, United States; Recruiting
Daniel Nikcevich, MD, PhD, Phone: 218-786-3625

Alegant Health Cancer Center at Bergan Mercy Medical Center, Omaha, Nebraska 68124, United States; Recruiting
Clinical Trials Office - Alegant Health Cancer Center at Berge, Phone: 402-398-6060

CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68106, United States; Recruiting
Gamini S. Soori, MD, FACP, FRCP, MBA, Phone: 402-393-3110

Creighton University Medical Center, Omaha, Nebraska 68131-2197, United States; Recruiting
Clinical Trials Office - Creighton University Medical Center, Phone: 402-280-4100

Immanuel Medical Center, Omaha, Nebraska 68122, United States; Recruiting
Gamini S. Soori, MD, FACP, FRCP, MBA, Phone: 402-393-3110

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States; Recruiting
Clinical Trials Office - Roswell Park Cancer Institute, Phone: 877-275-7724

Bismarck Cancer Center, Bismarck, North Dakota 58501, United States; Recruiting
Edward J. Wos, DO, Phone: 701-323-5741

Medcenter One Hospital Cancer Care Center, Bismarck, North Dakota 58501, United States; Recruiting
Edward J. Wos, DO, Phone: 701-323-5741

Mid Dakota Clinic, PC, Bismarck, North Dakota 58501, United States; Recruiting
Clinical Trials Office - Mid Dakota Clinic, PC, Phone: 701-530-6950

St. Alexius Medical Center Cancer Center, Bismarck, North Dakota 58502, United States; Recruiting
Clinical Trials Office - St. Alexius Medical Center Cancer Cen, Phone: 701-530-6950

Bryn Mawr Hospital, Bryn Mawr, Pennsylvania 19010, United States; Recruiting
Clinical Trials Office - Bryn Mawr Hospital, Phone: 610-645-2680

Cancer Center of Paoli Memorial Hospital, Paoli, Pennsylvania 19301-1792, United States; Recruiting
Clinical Trials Office - Cancer Center of Paoli Memorial Hospi, Phone: 610-648-1637

CCOP - Main Line Health, Wynnewood, Pennsylvania 19096, United States; Recruiting
Paul B. Gilman, MD, Phone: 610-645-2000

Lankenau Cancer Center at Lankenau Hospital, Wynnewood, Pennsylvania 19096, United States; Recruiting
Paul B. Gilman, MD, Phone: 610-645-2000

Allenmore Hospital, Tacoma, Washington 98405, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

Auburn Regional Center for Cancer Care, Auburn, Washington 98002, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

CCOP - Northwest, Tacoma, Washington 98405, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

Franciscan Cancer Center at St. Joseph Medical Center, Tacoma, Washington 98405-3004, United States; Recruiting
Clinical Trials Office - Franciscan Cancer Center, Phone: 253-426-6914

Good Samaritan Cancer Center, Puyallup, Washington 98372, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

MultiCare Regional Cancer Center at Tacoma General Hospital, Tacoma, Washington 98405, United States; Recruiting
Clinical Trials Office - MultiCare Regional Cancer Center, Phone: 253-403-3229

Providence Centralia Hospital, Centralia, Washington 98531-9027, United States; Recruiting
Clinical Trials Office - Providence Centralia H, Phone: 360-493-4300

Providence St. Peter Hospital Regional Cancer Center, Olympia, Washington 98506-5166, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

St. Clare Hospital, Tacoma, Washington 98499, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

St. Francis Hospital, Federal Way, Washington 98003, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1677

Marshfield Clinic - Indianhead Center, Rice Lake, Wisconsin 54868, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

Marshfield Clinic - Lakeland Center, Minocqua, Wisconsin 54548, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States; Recruiting
Clinical Trials Office - Marshfield Clinic - Marshfield Center, Phone: 800-782-1581 ext. 94457

Marshfield Clinic - Weston Center, Weston, Wisconsin 54476, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

Marshfield Clinic - Wisconsin Rapids Center, Wisconsin Rapids, Wisconsin 54494, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

Marshfield Clinic Cancer Care at Regional Cancer Center, Eau Claire, Wisconsin 54701, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

Ministry Medical Group at Saint Mary's Hospital, Rhinelander, Wisconsin 54501, United States; Recruiting
Matthias Weiss, MD, Phone: 715-358-1266

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

Starting date: February 2008
Last updated: October 17, 2009