Clinical trial NCT00002849: S9628 Dexamethasone Plus Interferon Alfa in Treating Patients With Primary Systemic Amyloidosis
Official title: Phase II Study of Dexamethasone/Alpha-Interferon in AL Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: primary systemic amyloidosis
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Cancer and Leukemia Group B
First posted: 2003-01-27
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Chemotherapy plus interferon alfa may be effective for primary systemic amyloidosis.

PURPOSE: Phase II trial to study the effectiveness of dexamethasone plus interferon alfa in treating patients who have primary systemic amyloidosis.

Detailed description: OBJECTIVES:

* Evaluate M protein and organ dysfunction responses and overall and progression-free survival in patients with primary systemic amyloidosis treated with dexamethasone/interferon alfa.
* Identify prognostic factors that may relate to response and overall survival in these patients.
* Evaluate the qualitative and quantitative toxic effects of this regimen.

OUTLINE: Patients are stratified by prior amyloidosis treatment (yes vs no).

All patients receive induction therapy with oral dexamethasone on days 1-4, 9-12, and 17-20 every 35 days for a total of 3 courses.

Maintenance therapy begins within 5-8 weeks (within 10 weeks if patients undergo stem cell harvest) of initiation of the third course of induction, as follows: oral dexamethasone for 4 days every 4 weeks; and subcutaneous interferon alfa 3 times per week. Patients who achieved less than a 50% reduction in serum M protein or urinary Bence-Jones protein and who experienced less than grade 3 toxicity during induction receive 3 additional courses of pulse dexamethasone concurrently with entry to maintenance therapy and the initiation of interferon alfa.

Combination therapy is continued until 2 years from entry; thereafter, interferon is administered alone for at least 3 years, toxicity permitting. Patients with stable disease after 5 years of therapy may discontinue interferon alfa at the discretion of the treating physician.

Patients are followed every 6 months for 2 years and yearly thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 with prior melphalan/prednisone or iododoxorubicin treatment and 50 without) will be entered over 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically diagnosed primary systemic amyloidosis based on the following:

  * Deposition of fibrillary protein with Congo red positive stain or characteristic electron microscopic appearance
  * Monoclonal light chain protein (Bence-Jones protein) in serum or urine or immunohistochemical studies
  * Evidence of tissue involvement other than carpal tunnel syndrome
  * Diagnostic histologic material available for central pathology review

    * Confirmation of tissue diagnosis at all sites of organ dysfunction encouraged
* No senile, secondary, localized, dialysis-related, or familial amyloidosis
* No known therapy-related myelodysplasia

PATIENT CHARACTERISTICS:

Age:

* Adult

Performance status:

* SWOG 0-4

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Cardiovascular:

* No NYHA class IV status

Other:

* No uncontrolled diabetes
* No active peptic ulcer disease
* No medical condition that precludes high-dose steroids
* No second malignancy within 5 years except:
* Adequately treated nonmelanomatous skin cancer
* In situ cervical cancer
* Adequately treated stage I/II cancer in complete remission
* Not pregnant or nursing
* Effective contraception required of fertile patients
* Blood/body fluid analyses within 14 days prior to registration
* Imaging/exams for tumor measurement within 28 days prior to registration
* Other screening exams within 42 days prior to registration

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior interferon alfa

Chemotherapy

* Prior melphalan allowed, but recovered from effects
* At least 4 weeks since cytotoxic therapy and recovered

Endocrine therapy

* Prior prednisone allowed, but recovered from effects
* At least 4 weeks since prior glucocorticoids
* No prior dexamethasone
* No planned or concurrent dexamethasone or other therapy for primary systemic amyloidosis

Radiotherapy

* Not specified

Surgery

* Not specified

Primary outcomes:
measure: response
timeFrame: 10 months
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
Study officials:
affiliation: University of Arkansas
name: Laura F. Hutchins, MD
role: STUDY_CHAIR
affiliation: University of Chicago
name: Richard A. Larson, MD
role: STUDY_CHAIR
References:
citation: Dhodapkar MV, Hussein MA, Rasmussen E, Solomon A, Larson RA, Crowley JJ, Barlogie B; United States Intergroup Trial Southwest Oncology Group. Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood. 2004 Dec 1;104(12):3520-6. doi: 10.1182/blood-2004-05-1924. Epub 2004 Aug 12.
citation: Dhodapkar M, Jacobson J, Hussein M, et al.: High dose dexamethasone (Dex) with maintenance Dex / alpha interferon leads to improved survival in patients with primary systemic amyloidosis: results of US Intergroup Trial Southwest Oncology Group (SWOG) S9628. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2278, 2003.