Combination Chemotherapy Followed By Vaccine Therapy Plus Sargramostim in Treating Patients With Stage III or Stage IV Non-Hodgkin's Lymphoma

NCT ID: NCT00017290

Last Updated: 2013-12-04

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

UNKNOWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2000-11-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vaccines may make the body build an immune response to kill cancer cells. It is not yet known which regimen of chemotherapy combined with vaccine therapy is more effective for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy followed by vaccine therapy plus sargramostim in treating patients who have stage III or stage IV non-Hodgkin's lymphoma.

Detailed Description

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OBJECTIVES:

* Compare the time to tumor progression in patients with stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with cyclophosphamide, prednisone, and vincristine followed by immunotherapy with keyhole limpet hemocyanin with or without autologous tumor-derived immunoglobulin idiotype and adjuvant sargramostim (GM-CSF).
* Compare the efficacy of these immunotherapy regimens in terms of converting patients with partial response or unconfirmed complete response to clinical complete response.
* Compare the safety and toxic effects of these immunotherapy regimens in this patient population.
* Compare the time to treatment failure and survival of patients treated with these regimens.
* Correlate the induction of idiotype-specific immune response with clinical benefits of achieving molecular remission in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study.

Patients receive cyclophosphamide IV over 30-40 minutes and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses.

At 6 months after completion of chemotherapy, patients maintaining partial response (PR), complete response (CR), or unconfirmed complete response (CRU) receive immunotherapy. Patients are stratified according to participating center and baseline disease status (PR vs CR/CRU). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive autologous tumor-derived immunoglobulin idiotype conjugated to keyhole limpet hemocyanin (KLH) subcutaneously (SC) on day 1 and adjuvant sargramostim (GM-CSF) SC on days 1-4 of weeks 0, 4, 8, 12, 16, 20, and 24.
* Arm II: Patients receive KLH alone SC on day 1 and GM-CSF SC on days 1-4 of weeks 0, 4, 8, 12, 16, 20, and 24.

Quality of life is assessed prior to first immunization, at 2-8 weeks after completion of immunizations, and then every 6 months for 30 months.

Patients are followed every 3 months for 1 year and then every 6 months thereafter. Patients also enroll in a long-term follow-up study for an additional 5 years.

PROJECTED ACCRUAL: A total of 360 patients (240 in arm I and 120 in arm II) will be accrued from the 480 patients biopsied for this study within 15-18 months.

Conditions

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Lymphoma

Keywords

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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

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

keyhole limpet hemocyanin

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically confirmed stage III or IV follicular B-cell non-Hodgkin's lymphoma
* At least 1 bidimensionally measurable lesion by radiography, in addition to lesion removed for biopsy
* No clinical evidence of CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 1,500/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.5 times upper limit of normal (ULN)
* Hepatitis B surface antigen negative
* Hepatitis C antibody negative

Renal:

* Creatinine less than 1.5 times ULN

Other:

* No other malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
* No history of autoimmune disease
* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior antibody therapy for lymphoma

Chemotherapy:

* No prior cytotoxic therapy for lymphoma

Endocrine therapy:

* No prior corticosteroids for lymphoma
* At least 12 months since prior corticosteroids or immunosuppressants for other conditions
* Prior transient corticosteroids (prior to CT imaging) or optical solutions allowed

Radiotherapy:

* Prior radiotherapy for lymphoma (no more than 2 sites of limited disease) allowed

Surgery:

* See Disease Characteristics

Other:

* No concurrent participation in other therapeutic clinical trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genitope Corporation

INDUSTRY

Sponsor Role lead

Principal Investigators

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David Hinds

Role: STUDY_CHAIR

Genitope Corporation

Locations

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SuperGen, Incorporated

Dublin, California, United States

Site Status

California Cancer Care, Inc.

Greenbrae, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Site Status

Rocky Mountain Cancer Centers - Midtown

Denver, Colorado, United States

Site Status

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

Mountain States Tumor Institute - Boise

Boise, Idaho, United States

Site Status

Rush Cancer Institute at Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Veterans Affairs Medical Center - Ann Arbor

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Sarah Cannon Cancer Center at Centennial Medical Center

Nashville, Tennessee, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

Toronto Sunnybrook Regional Cancer Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Levy R, Ganjoo KN, Leonard JP, Vose JM, Flinn IW, Ambinder RF, Connors JM, Berinstein NL, Belch AR, Bartlett NL, Nichols C, Emmanouilides CE, Timmerman JM, Gregory SA, Link BK, Inwards DJ, Freedman AS, Matous JV, Robertson MJ, Kunkel LA, Ingolia DE, Gentles AJ, Liu CL, Tibshirani R, Alizadeh AA, Denney DW Jr. Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. J Clin Oncol. 2014 Jun 10;32(17):1797-803. doi: 10.1200/JCO.2012.43.9273. Epub 2014 May 5.

Reference Type DERIVED
PMID: 24799467 (View on PubMed)

Other Identifiers

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GENITOPE-G2000-03

Identifier Type: -

Identifier Source: secondary_id

CUMC-0101-142

Identifier Type: -

Identifier Source: secondary_id

UCLA-0010061

Identifier Type: -

Identifier Source: secondary_id

CDR0000068673

Identifier Type: -

Identifier Source: org_study_id