Clinical trial NCT00089115: Vaccine Therapy and Sargramostim Compared With Placebo and Sargramostim Following Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lymphoma
Keywords: contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-08-05
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to progression after 248 patients have progressed
Secondary outcomes:
measure: Response rate improvement after 248 patients have progressed
measure: Overall complete response rate by modified Cheson Criteria after 248 patients have progressed
measure: Duration of response by modified Cheson Criteria after 248 patients have progressed
measure: Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Newport Beach
country: United States
facility: Hoag Cancer Center at Hoag Memorial Hospital Presbyterian
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Center - Kaiser Foundation Hospital - San Diego
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center - Vallejo
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Midtown
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants, P.A. at Helen F. Graham Cancer Center
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Boca Raton
country: United States
facility: Center for Hematology-Oncology - Boca Raton
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Coeur d'Alene
country: United States
facility: North Idaho Cancer Center
state: Idaho
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center - Philipps Ambulatory Care Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota Clinic, P. C.
state: North Dakota
city: Fargo
country: United States
facility: Roger Maris Cancer Center at MeritCare Hospital
state: North Dakota
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente Medical Office - Interstate Medical Office Central
state: Oregon
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase-Temple Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center at Centennial Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Network of South Texas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
Study officials:
affiliation: Favrille
name: John F. Bender, PharmD
role: STUDY_CHAIR
References:
citation: 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-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol. 2009 Jun 20;27(18):3036-43. doi: 10.1200/JCO.2008.19.8903. Epub 2009 May 4.