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

August 1, 2013 updated by: Favrille

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Comprehensive Cancer Center at University of Alabama at Birmingham
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Scottsdale
    • California
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research Foundation
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, United States, 90089
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Los Angeles, California, United States, 90048
        • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
      • Newport Beach, California, United States, 92663
        • Hoag Cancer Center at Hoag Memorial Hospital Presbyterian
      • San Diego, California, United States, 92120
        • Kaiser Permanente Medical Center - Kaiser Foundation Hospital - San Diego
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital Cancer Center
      • San Francisco, California, United States, 94143-0324
        • UCSF Comprehensive Cancer Center
      • Stanford, California, United States, 94305
        • Stanford Cancer Center at Stanford University Medical Center
      • Vallejo, California, United States, 94589
        • Kaiser Permanente Medical Center - Vallejo
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers - Denver Midtown
    • Delaware
      • Newark, Delaware, United States, 19713-2055
        • Medical Oncology Hematology Consultants, P.A. at Helen F. Graham Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Cancer Center at Georgetown University Medical Center
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Center for Hematology-Oncology - Boca Raton
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Science Center - Jacksonville
      • Tampa, Florida, United States, 33612-9497
        • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
    • Idaho
      • Coeur d'Alene, Idaho, United States, 83814
        • North Idaho Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0084
        • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Cancer Institute at Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, United States, 21204-6881
        • Greater Baltimore Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Detroit, Michigan, United States, 48202-2608
        • Josephine Ford Cancer Center at Henry Ford Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital
    • Montana
      • Missoula, Montana, United States, 59802
        • Montana Cancer Specialists at Montana Cancer Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Cancer Center
    • New York
      • Bronx, New York, United States, 10466-2604
        • Our Lady of Mercy Medical Center Comprehensive Cancer Center
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10003
        • Beth Israel Medical Center - Philipps Ambulatory Care Center
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • North Dakota
      • Bismarck, North Dakota, United States, 58502-5538
        • Mid Dakota Clinic, P. C.
      • Fargo, North Dakota, United States, 58122
        • Roger Maris Cancer Center at MeritCare Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Charles M. Barrett Cancer Center at University Hospital
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Cleveland, Ohio, United States, 44106-5047
        • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Cancer Center at Providence Portland Medical Center
      • Portland, Oregon, United States, 97239-3098
        • Cancer Institute at Oregon Health and Science University
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Medical Office - Interstate Medical Office Central
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822-0001
        • Geisinger Medical Center
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase-Temple Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15224
        • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center at Centennial Medical Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center - Dallas
      • Houston, Texas, United States, 77030-4009
        • M.D. Anderson Cancer Center at University of Texas
      • San Antonio, Texas, United States, 78229
        • Cancer Care Network of South Texas
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
      • Yakima, Washington, United States, 98902
        • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Comprehensive Cancer Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic - Marshfield Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time to progression after 248 patients have progressed

Secondary Outcome Measures

Outcome Measure
Response rate improvement after 248 patients have progressed
Overall complete response rate by modified Cheson Criteria after 248 patients have progressed
Duration of response by modified Cheson Criteria after 248 patients have progressed
Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Favrille

Investigators

  • Study Chair: John F. Bender, PharmD, Favrille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Study Registration Dates

First Submitted

August 4, 2004

First Submitted That Met QC Criteria

August 4, 2004

First Posted (Estimate)

August 5, 2004

Study Record Updates

Last Update Posted (Estimate)

August 2, 2013

Last Update Submitted That Met QC Criteria

August 1, 2013

Last Verified

February 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAV-ID-06
  • CDR0000378046 (Registry Identifier: PDQ (Physician Data Query))
  • FAV-WIRB-20040335
  • CWRU-FVID-1404

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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