GM-CSF With or Without Vaccine Therapy After Combination Chemotherapy and Rituximab as First-Line Therapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

December 17, 2013 updated by: Favrille

Phase III, Double-Blind, Randomized, Placebo-Controlled Trial of FavID® (Id/KLH) and GM-CSF Following CHOP/Rituximab as First-Line Therapy in Subjects With High-Intermediate and High-Risk Diffuse Large B-Cell Lymphoma

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Vaccines made from a person's cancer cells may help the body build an effective immune response to kill cancer cells. It is not yet known whether giving GM-CSF together with vaccine therapy is more effective than giving GM-CSF together with a placebo when given after combination chemotherapy and rituximab in treating diffuse large B-cell lymphoma.

PURPOSE: This randomized phase III trial is studying GM-CSF and vaccine therapy to see how well they work compared to GM-CSF and placebo when given after combination chemotherapy and rituximab as first-line therapy in treating patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the 3-year disease-free survival of patients with high-intermediate- or high-risk bulky stage II or stage III or IV diffuse large B-cell lymphoma treated with sargramostim (GM-CSF) with or without autologous immunoglobulin idiotype-KLH conjugate vaccine (FavId®) after combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R).

Secondary

  • Compare the 2-year disease-free survival, duration of response, time to progression, overall survival, and safety in patients treated with these regimens.
  • Estimate the rate of immune reactivity to FavId®.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to risk score (3 [high-intermediate] vs 4 or 5 [high]).

  • Chemotherapy: Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV, vincristine IV, and rituximab IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

  • Sargramostim (GM-CSF) with or without autologous immunoglobulin idiotype-KLH conjugate vaccine (FavId®): Patients achieving complete remission (CR) or unconfirmed CR after chemotherapy and who have FavId® available are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive FavId® 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 and GM-CSF SC as in arm I. In both arms, treatment repeats once a month for 6 months and then once every 2 months for 24 months (18 total vaccinations) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 480 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

480

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
    • California
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research Foundation
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

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 diffuse large B-cell lymphoma

    • Bulky stage II or stage III or IV disease
    • Treatment naïve
    • International Prognostic Index score of 3 (high-intermediate) or 4/5 (high)
  • Lymphoma accessible for sampling or existing biopsy material judged suitable for preparation of autologous immunoglobulin idiotype-KLH conjugate vaccine (FavId®)
  • No history of CNS lymphoma or meningeal lymphomatosis
  • No history of indolent lymphoma

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Platelet count > 75,000/mm^3
  • ALT and AST < 2 times upper limit of normal
  • Not pregnant or nursing
  • No history of unresolved hepatitis B viral infection
  • No history of a treated prior malignancy unless in remission ≥ 2 years, except for treated nonmelanoma carcinomas of the skin or in situ cervical carcinomas or prostatic carcinomas
  • No contraindication to doxorubicin hydrochloride (e.g., abnormal contractility on ECG)
  • No contraindication to vincristine (e.g., peripheral neuropathy)
  • No know HIV positivity

  • No serious nonmalignant disease, including any of the following:

    • Psychiatric disorders
    • Compromised pulmonary function
    • Congestive heart failure
    • Active bacterial, viral, or fungal infections

PRIOR CONCURRENT THERAPY:

  • No prior keyhole limpet hemocyanin
  • No planned radiotherapy during or after study therapy
  • No concurrent systemic immunosuppressive therapy (e.g., steroids)

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
Disease-free survival as measured by the Kaplan-Meier method at 3 years

Secondary Outcome Measures

Outcome Measure
Disease-free survival as measured by the Kaplan-Meier method at 2 years
Duration of response (complete or partial response)
Overall disease-free survival

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

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 Registration Dates

First Submitted

May 10, 2006

First Submitted That Met QC Criteria

May 10, 2006

First Posted (Estimate)

May 11, 2006

Study Record Updates

Last Update Posted (Estimate)

December 18, 2013

Last Update Submitted That Met QC Criteria

December 17, 2013

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000466677
  • FAV-ID-11
  • FAV-WIRB-20051774

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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