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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00040937
• Other study ID #: S0204
• Secondary ID: S0204U10CA032102
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 8, 2002
• Last updated: March 5, 2015
• Start date: June 2002
• Est. completion date: October 2015

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 147
• Est. completion date: October 2015
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• filgrastim
PBSC collection: 10 mcg/kg SQ days 1-10
• 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

Drug:
• cyclophosphamide
PBSC collection: 1 mg/m2 IV over 45-60 mins day 0
• dexamethasone
40 mg/d PO days 1-4, 9-12, 17-20
• melphalan
st trans: 140 mg/m2 IV over 20 mins day -1 nd trans: 200mg/m2 IV over 20 mins day -1
• prednisone
maint: 50 mg/d PO every other day until progression
• 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

Procedure:
• peripheral blood stem cell transplantation
2-4 x 10^6/kg IV day 0

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	Aiea	Hawaii
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Auburn Regional Center for Cancer Care	Auburn	Washington
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Bay Regional Medical Center	Bay City	Michigan
United States	St. Francis Hospital and Health Centers	Beech Grove	Indiana
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Mecosta County General Hospital	Big Rapids	Michigan
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Deaconess Billings Clinic Cancer Center	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Internal Medicine Associates of Bozeman	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Community Hospital	Butte	Montana
United States	Regional Cancer Center at Providence Hospital	Centralia	Washington
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Riverside Cancer Services	Columbus	Ohio
United States	Mount Carmel West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	University of California Davis Cancer Center	Davis	California
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Grady Memorial Hospital	Delaware	Ohio
United States	St. Francis Hospital	Federal Way	Washington
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Legacy Mount Hood Medical Center	Glesham	Oregon
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan
United States	Metropolitan Hospital	Grand Rapids	Michigan
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Sletten Regional Cancer Institute	Great Falls	Montana
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Cancer Research Center of Hawaii	Honolula	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	St. Francis Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	UMC Southwest Cancer and Research Center	Lubbock	Texas
United States	MedCentral - Mansfield Hospital	Mansfield	Ohio
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Eastern Montana Cancer Center	Miles City	Montana
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Community Medical Center	Missoula	Montana
United States	Judy L. Schmidt, MD, FACP, P. C.	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	Hackley Hospital	Muskegon	Michigan
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Capital Medical Center	Olympia	Washington
United States	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington
United States	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center	Portland	Oregon
United States	Institute of Oncology at Vilnius University	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Sutter Roseville Medical Center	Roseville	California
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Sutter Cancer Center	Sacramento	California
United States	Salina Regional Health Center	Salina	Kansas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center Oncology Unit	Springfield	Ohio
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	St. Joseph Medical Center at Franciscan Health System	Tacoma	Washington
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas
United States	Stormont-Vail Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Central Washington Hospital	Wenatchee	Washington
United States	Wenatchee Valley Clinic	Wenatchee	Washington
United States	Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital	Westerville	Ohio
United States	Wesley Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	United States Air Force Medical Center Wright-Patterson	Wright-Patterson Afb	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		4-7 years	No
Secondary	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	Yes