S0204 Thalidomide, Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

A Phase II Trial Of Thalidomide/Dexamethasone Induction Followed By Tandem Melphalan Transplant And Prednisone/Thalidomide Maintenance (A BMT Study)

RATIONALE: Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving thalidomide before and after peripheral stem cell transplant may be effective in treating newly diagnosed multiple myeloma.

PURPOSE: This phase II trial is studying how well giving thalidomide with chemotherapy and peripheral stem cell transplant work in treating patients with newly diagnosed multiple myeloma.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: filgrastim; Biological: sargramostim; Drug: cyclophosphamide; Drug: dexamethasone; Drug: melphalan; Drug: prednisone; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation

Detailed Description

OBJECTIVES:

• Determine the efficacy and toxicity of thalidomide and dexamethasone as a pre-transplantation induction regimen in patients with multiple myeloma.
• Determine, preliminarily, the safety and efficacy of prednisone and thalidomide maintenance therapy in these patients.
• Correlate chromosome 13 abnormalities with therapeutic response in patients treated with this regimen.
• Correlate specific subsets of chromosome aberrations with event-free and overall survival of patients treated with this regimen.
• Evaluate immune reconstitution and recovery after first and second transplantation in these patients.

OUTLINE: This is a multicenter study.

• Induction chemotherapy: Patients receive oral thalidomide once daily on days 1-35 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 35 days for 3 courses in the absence of disease progression or unacceptable toxicity.
• Stem cell mobilization and collection: Beginning 5-7 days, but no more than 3 weeks, after completion of induction chemotherapy, patients receive cyclophosphamide IV over 45-60 minutes on day 0, filgrastim (G-CSF) subcutaneously (SC) on days 1-10, and sargramostim (GM-CSF) SC beginning on day 1 and continuing until completion of peripheral blood stem cell (PBSC) collection. Patients begin PBSC collection on day 11 or as soon as blood counts recover.
• First transplantation: Within 3-6 weeks after cyclophosphamide administration, patients receive melphalan IV over 20 minutes on day -1. Patients undergo PBSC infusion on day 0. Patients receive GM-CSF SC or IV beginning on day 6 and continuing until blood counts recover.
• Second transplantation: Between 2-4 months after first transplantation, patients undergo a second tandem melphalan and PBSC transplantation with GM-CSF support as above.
• Maintenance therapy: Beginning 70-90 days post-transplantation, patients receive oral prednisone every other day and oral thalidomide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 12 months for 10 years.

PROJECTED ACCRUAL: Approximately 99 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Davis, California, United States, 95616
      • University of California Davis Cancer Center
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30342
      • CCOP - Atlanta Regional
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital Cancer Center
    • Austell, Georgia, United States, 30106
      • WellStar Cobb Hospital
    • Decatur, Georgia, United States, 30033
      • Charles B. Eberhart Cancer Center at DeKalb Medical Center
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
    • Marietta, Georgia, United States, 30060
      • Kennestone Cancer Center at Wellstar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
  • Hawaii
    • Aiea, Hawaii, United States, 96701
      • Kapiolani Medical Center at Pali Momi
    • Honolula, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • OnCare Hawaii, Incorporated - Lusitana
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Institute at Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital, Incorporated
    • Honolulu, Hawaii, United States, 96817
      • OnCare Hawaii, Incorporated - Kuakini
    • Honolulu, Hawaii, United States, 96817
      • St. Francis Medical Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Mountain States Tumor Institute - Boise
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Cancer Center
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Louisiana
    • Monroe, Louisiana, United States, 71210
      • Louisiana State University Health Sciences Center - Monroe
    • Shreveport, Louisiana, United States, 71130
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Bay City, Michigan, United States, 48708
      • Bay Regional Medical Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County General Hospital
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Mercy Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Cancer Care - Butterworth Campus
    • Grand Rapids, Michigan, United States, 49506
      • Metropolitan Hospital
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49443
      • Hackley Hospital
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinic - Downtown
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
    • Billings, Montana, United States, 59107
      • Deaconess Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Internal Medicine Associates of Bozeman
    • Butte, Montana, United States, 59701
      • St. James Community Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Miles City, Montana, United States, 59301
      • Eastern Montana Cancer Center
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59802
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59804
      • Judy L. Schmidt, MD, FACP, P. C.
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Chillicothe, Ohio, United States, 54601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43215
      • Grant Riverside Cancer Services
    • Columbus, Ohio, United States, 43222
      • Mount Carmel West Hospital
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center Oncology Unit
    • Troy, Ohio, United States, 45373
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
    • Wright-Patterson Afb, Ohio, United States, 45433-5529
      • United States Air Force Medical Center Wright-Patterson
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • Oregon
    • Glesham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97210
      • Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97227
      • Institute of Oncology at Vilnius University
    • Portland, Oregon, United States, 97239
      • Cancer Institute at Oregon Health and Science University
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Rose Ramer Cancer Clinic at Anderson Area Medical Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29304
      • CCOP - Upstate Carolina
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Lackland AFB, Texas, United States, 78236
      • Wilford Hall Medical Center
    • Lubbock, Texas, United States, 79415
      • UMC Southwest Cancer and Research Center
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Hospital Community Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531
      • Regional Cancer Center at Providence Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Olympia, Washington, United States, 98507
      • Capital Medical Center
    • Olympia, Washington, United States, 95806
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98114
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Sedro-Wooley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
    • Tacoma, Washington, United States, 98405
      • St. Joseph Medical Center at Franciscan Health System
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Wenatchee, Washington, United States, 98801
      • Central Washington Hospital
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Clinic
  • West Virginia
    • Parkersburg, West Virginia, United States, 26101
      • Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma requiring treatment

  • Smoldering myeloma with evidence of progressive disease requiring chemotherapy

    • More than 25% increase in M component levels and/or Bence-Jones excretion or symptom development
  • Non-secretory patients with at least 30% bone marrow plasmacytosis
• No IgM peaks unless there is evidence of more than 30% bone marrow plasmacytosis or more than 3 lytic lesions

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• Zubrod 0-2 OR
• Zubrod 3-4 based solely on bone pain

Life expectancy

• Not specified

Hematopoietic

• No untreated, unresolved symptomatic hyperviscosity

Hepatic

• Hepatitis B negative

Renal

• Creatinine no greater than 3 mg/dL if in renal failure and on dialysis (after hydration and/or correction of hypercalcemia)

Cardiovascular

• No history of chronic cerebrovascular accident
• No myocardial infarction within the past 6 months
• No unstable angina
• No congestive heart failure that is difficult to control
• No uncontrollable hypertension
• No cardiac arrhythmia that is difficult to control

Pulmonary

• No history of chronic obstructive or chronic restrictive pulmonary disease
• No untreated, unresolved pneumonia
• Pulmonary function tests (PFTs) at least 50% of predicted
• DLCO at least 50% of predicted
• Arterial partial pressure of oxygen greater than 70 if unable to complete PFTs due to bone pain or fracture

Other

• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No untreated, unresolved pathologic fractures
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use at least 2 highly effective methods of contraception for 4 weeks before, during, and for at least 4 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No more than 8 weeks of prior thalidomide therapy

Chemotherapy

• No prior chemotherapy for this disease

Endocrine therapy

• Prior steroid therapy allowed provided treatment duration was no more than 2 weeks

Radiotherapy

• No prior radiotherapy to more than 50% of the pelvis

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment arm; thalidomide/dexamethasone followed by tandem melphalan peripheral blood stem cell transplantation (with cyclophosphamide and filgrastim or sargramostim support) and prednisone/thalidomide maintenance

Biological: filgrastim; PBSC collection: 10 mcg/kg SQ days 1-10; Other Names: G-CSF; Biological: sargramostim; PBSC collection: 500 mcg/m2 SQ day 1 through last apheresis 1st and 2nd trans: 500 mcg SC or IV days 6-WBC recovery; Other Names: GM-CSF; Drug: cyclophosphamide; PBSC collection: 1 mg/m2 IV over 45-60 mins day 0; Other Names: cytoxan; Drug: dexamethasone; 40 mg/d PO days 1-4, 9-12, 17-20; Other Names: decadron; Drug: melphalan; st trans: 140 mg/m2 IV over 20 mins day -1; nd trans: 200mg/m2 IV over 20 mins day -1; Drug: prednisone; maint: 50 mg/d PO every other day until progression; Other Names: steroid; Drug: thalidomide; ind: 50 mg increased by 50 mg every week to max 400 mg PO qhs for 35 days maint: 50 mg/d increased by 50 mg every week to 200 mg PO daily until progression; Other Names: thalomid; Procedure: peripheral blood stem cell transplantation; 2-4 x 10^6/kg IV day 0; Other Names: stem cell transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	4-7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Toxicity of Thalidomide/Dexamethasone as a Pre-transplant Induction Regimen.	To assess Grade 3-5 AE related to thalidomide/dexamethasone when administered as a pre-transplant induction regimen.	Induction

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Mohamad A. Hussein, MD, The Cleveland Clinic

Publications and helpful links

General Publications

• Hussein MA, Bolejack V, Zonder JA, Durie BG, Jakubowiak AJ, Crowley JJ, Barlogie B. Phase II study of thalidomide plus dexamethasone induction followed by tandem melphalan-based autotransplantation and thalidomide-plus-prednisone maintenance for untreated multiple myeloma: a southwest oncology group trial (S0204). J Clin Oncol. 2009 Jul 20;27(21):3510-7. doi: 10.1200/JCO.2008.19.9240. Epub 2009 Jun 22.
• Hussein MA, Jakubowiak AJ, Bolejack V, et al.: S0204: melphalan (MEL)-based tandem autotransplants (TAT) for multiple myeloma (MM) with thalidomide/dexamethasone (TD) induction and thalidomide/prednisone (TP) maintenance: a phase II trial of the Southwest Oncology Group. [Abstract] Blood 108 (11): A-3088, 2006.

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: July 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Cyclophosphamide; Thalidomide; Prednisone; Melphalan; Sargramostim
• Other Study ID Numbers: S0204 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)