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

Sponsor

Genitope Corporation (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00017290

Collaborator

(none)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine Biological: keyhole limpet hemocyanin Biological: sargramostim Drug: cyclophosphamide Drug: prednisone Drug: vincristine sulfate	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SuperGen, Incorporated	Dublin	California	United States	94568
2	California Cancer Care, Inc.	Greenbrae	California	United States	94904
3	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
4	Stanford Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305-5151
5	Rocky Mountain Cancer Centers - Midtown	Denver	Colorado	United States	80218
6	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida	United States	32610-0277
7	Mountain States Tumor Institute - Boise	Boise	Idaho	United States	83712
8	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois	United States	60612
9	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
10	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
11	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
12	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
13	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105-2399
14	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
15	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
16	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
17	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
19	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
20	Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97201-3098
21	Sarah Cannon Cancer Center at Centennial Medical Center	Nashville	Tennessee	United States	37203
22	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
23	British Columbia Cancer Agency	Vancouver	British Columbia	Canada	V5Z 4E6
24	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario	Canada	M4N 3M5