Vaccine Therapy and Sargramostim Compared With Placebo and Sargramostim Following Rituximab in Treating Patients With Non-Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Phase III, Randomized, Double Blind, Placebo-Controlled Trial of Favldand GM-CSF Versus Placebo and GM-CSF Following Rituximab in Subjects With Follicular B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00089115
• Other study ID #: FAV-ID-06
• Secondary ID: CDR0000378046FAV
• Status: Terminated
• Phase: Phase 3
• First received: August 4, 2004
• Last updated: August 1, 2013
• Start date: July 2004

Study information

• Verified date: February 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Colony-stimulating factors such as GM-CSF increase the number of immune cells found in bone marrow and peripheral blood. It is not yet known whether combining rituximab and GM-CSF with vaccine therapy may cause a stronger immune response and kill more cancer cells.

PURPOSE: This randomized phase III trial is studying giving rituximab and GM-CSF together with vaccine therapy and comparing it to giving rituximab and GM-CSF alone in treating patients with newly diagnosed, relapsed, or refractory B-cell non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

Primary

• Compare time to disease progression in patients with grade 1, 2, or 3 follicular B-cell non-Hodgkin's lymphoma who respond (i.e., complete or partial response, or stable disease) to treatment with rituximab and are then treated with sargramostim (GM-CSF) with vs without autologous immunoglobulin idiotype-KLH conjugate vaccine.

Secondary

• Compare response rate improvement in patients treated with these regimens.

• Compare overall complete response rate in patients treated with these regimens.

• Compare duration of response in patients treated with these regimens.

• Determine the safety of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior treatment (yes vs no) and response to rituximab during study (complete response [CR] or partial response [PR] vs stable disease [SD]).

All patients receive rituximab IV once weekly for 4 weeks. Five weeks after the last dose of rituximab, patients are assessed for response. Patients with progressive disease are removed from the study and do not undergo randomization. Patients with a CR, PR, or SD are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine subcutaneously (SC) on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4.

• Arm II: Patients receive placebo SC on day 1. Patients also receive GM-CSF SC on days 1-4.

In both arms, treatment repeats monthly for 6 months in the absence of unacceptable toxicity or clinically significant progressive disease. After the first 6 months, patients with a CR, PR, or SD may continue to receive treatment (per treatment arm as above) every 2 months for 1 year (total of 6 doses) and then every 3 months thereafter in the absence of disease progression.

Patients are followed every 3 months for 2 years and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 342 evaluable patients (171 per treatment arm) will be accrued for this study within 18 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)

• Grade 1, 2, or 3

• Meets 1 of the following criteria for treatment with rituximab:

• Treatment naïve

• Relapsed or refractory disease after prior chemotherapy

• Relapsed after a prior documented response (i.e., complete or partial response) to rituximab of at least 6 months duration

• Tumor accessible for biopsy OR existing biopsy material (taken within the past 6 months) suitable for vaccine preparation

• Measurable or evaluable disease after tumor tissue procurement for vaccine production

• No more than 2 prior treatment regimens for NHL

• Single regimens include any of the following:

• Maintenance rituximab

• Rituximab administered once weekly for 8 courses

• Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab* NOTE: *CHOP followed by rituximab at time of relapse is considered 2 treatment regimens

• No history of CNS lymphoma or meningeal lymphomatosis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count = 1,500/mm^3

• Platelet count = 75,000/mm^3 (unless related to bone marrow involvement by lymphoma)

• Hemoglobin = 10g/dL

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No congestive heart failure

Pulmonary

• No compromised pulmonary function

Immunologic

• HIV negative

• No prior allergic response to GM-CSF

• No active bacterial, viral, or fungal infection

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No psychiatric disorder that would preclude study participation

• No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

• No other serious nonmalignant disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• See Chemotherapy

• At least 4 weeks since prior immunotherapy

• No prior radiolabeled anti-lymphoma antibody (e.g., iodine I 131 tositumomab or ibritumomab tiuxetan)

• No prior autologous or allogeneic stem cell transplantation

• No prior lymphoma-specific idiotype immunotherapy (e.g., Id vaccine)

• No prior investigational vaccine or immunotherapeutic containing keyhole limpet hemocyanin (KLH)

Chemotherapy

• See Disease Characteristics

• At least 4 weeks since prior chemotherapy

• More than 9 months since prior fludarabine

• More than 2 years since prior chemotherapy/rituximab combination therapy (e.g., CHOP/rituximab or cyclophosphamide, vincristine, and prednisone [CVP]/rituximab)

• No more than 6 total prior treatment courses with fludarabine

Endocrine therapy

• No concurrent steroids for allergic reaction to sargramostim (GM-CSF)

Radiotherapy

• See Biologic therapy

• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior experimental therapy

• No concurrent systemic immunosuppressive therapy

• No other concurrent anti-lymphoma therapy

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• autologous immunoglobulin idiotype-KLH conjugate vaccine

• rituximab

• sargramostim

Locations

Country	Name	City	State
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Mid Dakota Clinic, P. C.	Bismarck	North Dakota
United States	Center for Hematology-Oncology - Boca Raton	Boca Raton	Florida
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Baylor University Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Rocky Mountain Cancer Centers - Denver Midtown	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Sarah Cannon Cancer Center at Centennial Medical Center	Nashville	Tennessee
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Beth Israel Medical Center - Philipps Ambulatory Care Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Medical Oncology Hematology Consultants, P.A. at Helen F. Graham Cancer Center	Newark	Delaware
United States	Hoag Cancer Center at Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Fox Chase-Temple Cancer Center	Philadelphia	Pennsylvania
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Kaiser Permanente Medical Office - Interstate Medical Office Central	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Cancer Care Network of South Texas	San Antonio	Texas
United States	Kaiser Permanente Medical Center - Kaiser Foundation Hospital - San Diego	San Diego	California
United States	Sharp Memorial Hospital Cancer Center	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Favrille

Country where clinical trial is conducted

United States, 

References & Publications (1)

Freedman A, Neelapu SS, Nichols C, Robertson MJ, Djulbegovic B, Winter JN, Bender JF, Gold DP, Ghalie RG, Stewart ME, Esquibel V, Hamlin P. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophag — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression after 248 patients have progressed			No
Secondary	Response rate improvement after 248 patients have progressed			No
Secondary	Overall complete response rate by modified Cheson Criteria after 248 patients have progressed			No
Secondary	Duration of response by modified Cheson Criteria after 248 patients have progressed			No
Secondary	Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed			Yes