Protocol Number: 00-C-0050

Title:

Randomized Trial of Patient-Specific Vaccination with Conjugated Follicular Lymphoma-Derived Idiotype with Local GM-CSF in First Complete Remission

Number:

00-C-0050

Summary:

This study will evaluate the effectiveness of an experimental cancer vaccine for lymphoma. Although currently available lymphoma treatments (radiation therapy and various chemotherapy regimens) may cause a remission of disease, none provides a long-term survival.

Patients with lymphoma of the follicular, low-grade type may be eligible for this study. Those enrolled will undergo lymph node biopsy and bone marrow aspiration before beginning treatment. The biopsy involves surgically removing a lymph node from the neck, axilla, or groin. For the bone marrow test, a needle is inserted into the pelvic bone after the skin over the area has been numbed. A sample of bone marrow (blood and tissue) is then withdrawn through the needle. A bone marrow biopsy, in which a piece of the marrow tissue is removed, is done at the same time. After these procedures, patients will start chemotherapy with four drugs prednisone, adriamycin, cytoxan and etoposide administered in 28-day treatment cycles, as follows: Prednisone is taken by mouth days 1-14 of the cycle; the remaining three drugs are given intravenously (through a vein) on day 1 and day 8. No medicine is taken from days 15 to 28. Chemotherapy will continue until the entire tumor is gone or has stopped shrinking (this usually requires 6 to 8 cycles). At the completion of chemotherapy, patients are randomly assigned to one of two vaccination groups:

1. Group I (Id/KLH) Patients in group I will receive injections of a vaccine composed of a protein custom-made from their own tumor cells and another protein called KLH, which, linked to the tumor protein, may help produce an immune response to the tumor.

2. Group II (KLH) Patients in Group II will receive injections of KLH alone.

The first vaccination will be given 6 months after chemotherapy ends and will be repeated after 1, 2, 3 and 5 months. The vaccinations will be injected under the skin twice a day. Patients will also receive daily injections of GM-CSF, a growth factor naturally produced by bone marrow that can boost the immune system. These injections will be given the same day as vaccination and for the next 3 days.

A second lymph node biopsy may be requested during vaccine treatment. Bone marrow biopsies and aspirates will be repeated after 4, 6 and 8 months of chemotherapy and again at the beginning and end of vaccine therapy to examine the effects of treatment on the tumor and possible side effects of therapy on the bone marrow. Several blood tests will be done before, during and after therapy to monitor the effects of treatment. Leukapheresis a procedure for collecting white blood cells may be done just before beginning chemotherapy and again before beginning vaccine therapy to study T cells (a type of white blood cell important in the immune system). In this procedure, which is similar to donating whole blood, the blood is drawn through a vein and then flows into a cell separator machine, where the white cells are separated and removed. The rest of the blood is then returned to the patient.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Tissue diagnosis of follicular lymphoma with surface IgM or IgG phenotype with a monoclonal heavy and light chain as determined by Flow Cytometry. When a lymph node is biopsied to produce a vaccine, the NCI will histologically evaluate it. The histology of the biopsy must be Follicular Center Cell (FCC) grade I, II, or IIIa (follicular small-cleaved cell lymphoma, follicular mixed, or follicular large cell lymphoma with centrocytes).

Stage II with bulky adenopathy (greater than 5 cm in diameter), Stage III or IV lymphoma.

Only chemotherapy naive patients are eligible. Patients may have received Prednisone (less than two months of therapy)

Previous treatment with radiation alone (less than or equal to 2 sites) is permissible.

A single peripheral lymph node greater than 2 cm size accessible for biopsy/harvest or an abdominal lymph node greater than 2 cm that is accessible for laparoscopic biopsy. Patients with Lymphoma cells circulating in the peripheral blood, maligant pleural effusions, or malignant ascites may be eligible if adequate lymphoma cells are present (greater than 10(9)).

ECOG performance status less than 2, unless the performance is directly related to disease and therefore should improve with therapy.

Life expectancy of greater than one year.

Serum creatinine less than or equal to 1.5 mg/dl unless felt to be secondary to lymphoma.

Bilirubin less than or equal to 1.5 mg/dl unless felt to be secondary to lymphoma or Gilbert's disease. SGOT/SGPT less than or equal to 3.5 x upper limit of normal.

Ability to give informed consent. Ability to return to clinic for adequate follow-up for the period that the protocol requires.

EXCLUSION CRITERIA

Any amount of radiation exceeding 2 sites, including prior total body irradiation (TBI).

Presence of antibodies to HIV, hepatitis B surface antigen or other active infectious process. HIV supresses the immune system and causes other abnormalities of immunoregulation. Active infectious processes, including Hepatitis B, also cause abnormalities of immunorelation. This could potentially interfere with the development of an immune response to the tumor antigen.

Pregnancy or lactation. Chemotherapeutic agents are known to have teratogenic effects on developing embryos and to cause chromosomal damage to gametes. These agents also cause bone marrow suppression and can be excreted in milk. The effects of this type of vaccine on developing embryos is unknown. Since this therapy is not known to be curative, the potential risks to a fetus surpasses that of recognized benefit to the patient.

Fertile men and women must plan to use effective contraception. A beta-HCG level will be obtained in women of childbearing potential.

A history of unrelated (non-lymphomatous) neoplasm within the past 10 years other than non-melanoma skin cancer or in-situ cervix cancer. Patients with a prior diagnosis of malignancy more than 10 years may be entered into the study at the discretion of the Principal Investigator.

Patients unwilling to give informed consent.

Failure to meet any of the eligibility criteria.

Any medical or psychiatric condition that in the opinion of the protocol chairman would compromise the patient's ability to tolerate this treatment.

Patient with primary or secondary CNS lymphoma (current or previously treated) will not be eligible.

Special Instructions: Currently Not Provided

Keywords:

Adjuvant

Immunotherapy

Survival

Autologous

Chemotherapy

Recruitment Keywords:

None

Conditions:

B Cell Lymphoma

Follicular Lymphoma

Investigational Drug(s):

Id-KLH Vaccine

GM-CSF (Sargramostim)

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

"Good risk" non-Hodgkin's lymphomas: Approaches to management

No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types

The natural history of inially untreated low-grade non-Hodgkin's lymphomas

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