Clinical trial NCT00017290: Combination Chemotherapy Followed By Vaccine Therapy Plus Sargramostim in Treating Patients With Stage III or Stage IV Non-Hodgkin's Lymphoma
Official title: A Phase III Trial To Evaluate The Safety And Efficacy Of Specific Immunotherapy, Recombinant Idiotype Conjugated To KLH With GM-CSF, Compared To Non-Specific Immunotherapy, KLH With GM-CSF, In Patients With Follicular Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Dublin
country: United States
facility: SuperGen, Incorporated
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Midtown
state: Colorado
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida Health Science Center
state: Florida
city: Boise
country: United States
facility: Mountain States Tumor Institute - Boise
state: Idaho
city: Chicago
country: United States
facility: Rush Cancer Institute at Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: Veterans Affairs Medical Center - Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center at Centennial Medical Center
state: Tennessee
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
Study officials:
affiliation: Genitope Corporation
name: David Hinds
role: STUDY_CHAIR
References:
citation: 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.