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

NCT ID: NCT00089115

Last Updated: 2013-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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autologous immunoglobulin idiotype-KLH conjugate vaccine

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Favrille

INDUSTRY

Sponsor Role lead

Principal Investigators

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John F. Bender, PharmD

Role: STUDY_CHAIR

Favrille

Locations

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Comprehensive Cancer Center at University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Hoag Cancer Center at Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Kaiser Permanente Medical Center - Kaiser Foundation Hospital - San Diego

San Diego, California, United States

Site Status

Sharp Memorial Hospital Cancer Center

San Diego, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Site Status

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, United States

Site Status

Rocky Mountain Cancer Centers - Denver Midtown

Denver, Colorado, United States

Site Status

Medical Oncology Hematology Consultants, P.A. at Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

Lombardi Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Center for Hematology-Oncology - Boca Raton

Boca Raton, Florida, United States

Site Status

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Site Status

North Idaho Cancer Center

Coeur d'Alene, Idaho, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Site Status

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Site Status

New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Beth Israel Medical Center - Philipps Ambulatory Care Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

Our Lady of Mercy Medical Center Comprehensive Cancer Center

The Bronx, New York, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Mid Dakota Clinic, P. C.

Bismarck, North Dakota, United States

Site Status

Roger Maris Cancer Center at MeritCare Hospital

Fargo, North Dakota, United States

Site Status

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Site Status

Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, United States

Site Status

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Kaiser Permanente Medical Office - Interstate Medical Office Central

Portland, Oregon, United States

Site Status

Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Fox Chase-Temple Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Cannon Cancer Center at Centennial Medical Center

Nashville, Tennessee, United States

Site Status

Baylor University Medical Center - Dallas

Dallas, Texas, United States

Site Status

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Cancer Care Network of South Texas

San Antonio, Texas, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Site Status

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 19414675 (View on PubMed)

Other Identifiers

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CDR0000378046

Identifier Type: REGISTRY

Identifier Source: secondary_id

FAV-WIRB-20040335

Identifier Type: -

Identifier Source: secondary_id

CWRU-FVID-1404

Identifier Type: -

Identifier Source: secondary_id

FAV-ID-06

Identifier Type: -

Identifier Source: org_study_id