S9805, High-Dose Melphalan Plus Peripheral Stem Cell Transplantation Followed by Interferon Alfa in Treating Patients With Waldenstrom's Macroglobulinemia

Lymphoma Clinical Trial

Official title:

S9805, Phase II Study of Tandem High Dose Melphalan Supported by Peripheral Blood Stem Cell Support in Waldenstrom's Macroglobulinemia (WM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003416
• Other study ID #: S9805
• Secondary ID: S9805U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: March 5, 2015
• Start date: September 1998
• Est. completion date: January 2004

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: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. Interferon alfa may interfere with the growth of the cancer cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose melphalan plus peripheral stem cell transplantation followed by interferon alfa in treating patients with Waldenstrom's macroglobulinemia.

Description:

OBJECTIVES: I. Assess remission rates and overall and progression-free survival in patients with Waldenstrom's macroglobulinemia treated with tandem high dose melphalan supported by peripheral blood stem cell support. II. Assess the associated hematologic and nonhematologic toxicities of this regimen in these patients.

OUTLINE: Regimen A (dexamethasone induction): All patients receive high dose dexamethasone orally on days 1-4, 9-12, and 17-20; courses repeat every 35 days for a total of 3 courses. Regimen B (stem cell mobilization and collection): Following a 4-6 week break after dexamethasone induction and regardless of response or progression, patients have stem cells collected following administration of filgrastim (G-CSF) by injection; G-CSF continues until completion of stem cell collection (maximum of 6 aphereses). Regimen C (first peripheral blood stem cell transplant (PBSCT)): Regardless of disease progression, patients recovered from toxicities from dexamethasone induction and stem cell mobilization and collection, and who have adequate number of CD34 cells collected for at least 1 transplant, receive 1 dose of melphalan daily for 2 days followed by peripheral stem cell reinfusion. G-CSF is given by injection beginning on the day after peripheral stem cell reinfusion and continues until the absolute granulocyte count is greater than 1,000/mm3 on 3 consecutive days. Regimen D (second PBSCT): Patients who had adequate stem cell collection for 2 transplants during regimen B, have no evidence of disease progression after the first transplant, and have recovered from effects of previous treatment undergo a second treatment with high dose melphalan with PBSCT and G-CSF support, given 3-12 months following the first transplant. Patients who had enough cells collected for only one transplant go directly to regimen E. Regimen E (maintenance interferon alfa): Beginning 5-12 weeks after transplant and upon hematologic recovery of blood counts and other toxicities, patients with at least a partial response after high dose melphalan and PBSCT receive subcutaneous interferon alfa injections 3 times a week for 5 years or until disease progression, relapse, or toxicity. Patients are followed every month for 6 months, then every 3 months for 5 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study over 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: January 2004
• Est. primary completion date: August 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 69 Years

Eligibility

DISEASE CHARACTERISTICS: Immunologically diagnosed Waldenstrom's macroglobulinemia (WM) Evaluable quantifiable IgM One of the following criteria must be met: 1) Patient demonstrates clinical symptoms such as fatigue, dizziness, visual inacuity, or hemorrhagic manifestations of WM with anemia, hyperviscosity, thrombocytopenia, or coagulopathies 2) Advanced tumor mass present involving ONE of the following: Extensive lymphadenopathy (greater than 2 cm) Hepato or splenomegaly palpable on clinical examination Marked bone marrow infiltration greater than 50% 3) Progressive disease; i.e., increase in IgM concentration by at least 50%, and/or a drop of greater than 2 g/dL in hemoglobin (in the absence of gastrointestinal bleeding), and/or a greater than 50,000/mm3 decrease in platelets

PATIENT CHARACTERISTICS: Age: Under 70 Performance status: SWOG 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified Cardiovascular: At least 6 months since myocardial infarction No congestive heart failure No arrhythmia refractory to therapy Ejection fraction within normal range by MUGA or ECHO Pulmonary: FEV1 at least 50% of predicted DLCO at least 50% of predicted Other: Not pregnant or nursing Effective contraception required of fertile patients No significant comorbid condition No uncontrolled life-threatening infection No uncontrolled diabetes No other malignancy within past 5 years except adequately treated basal or squamous cell skin cancer, carcinoma in situ of the cervix or adequately treated stage I or II cancer currently in remission HIV negative Hepatitis B surface antigen negative

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since radiotherapy and recovered Surgery: Not specified

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Biological:
• filgrastim

• recombinant interferon alfa

Drug:
• dexamethasone

• melphalan

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Research & Treatment Center	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi
United States	Boston Medical Center	Boston	Massachusetts
United States	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	Beckman Research Institute, City of Hope	Duarte	California
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts
United States	CCOP - Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	CCOP - Dayton	Kettering	Ohio
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	MBCCOP - University of South Alabama	Mobile	Alabama
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Hospital - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Central Illinois	Springfield	Illinois
United States	CCOP - Northwest	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	confirmed remission rate		until death	No
Primary	overall survival (OS)		until death	No
Primary	progression free survival (PFS)		until death	No
Primary	toxicity		until death	Yes