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. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial of vaccine therapy plus sargramostim following chemotherapy in treating patients who have previously untreated aggressive non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
Lymphoma	Drug: autologous tumor cell vaccine  Drug: cyclophosphamide  Drug: doxorubicin  Drug: keyhole limpet hemocyanin  Drug: mitoxantrone  Drug: prednisone  Drug: sargramostim  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the ability of recombinant idiotype immunotherapy to stimulate a specific immune response against the B cell idiotype of the malignant clone that constitutes the tumor in patients with previously untreated aggressive non-Hodgkin's lymphoma.

II. Determine the safety and toxicity of this treatment regimen using Genitope Corporation's molecular rescue technology in this patient population.

PROTOCOL OUTLINE: Patients receive induction chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). Treatment repeats every 3 weeks until the maximal clinical response is achieved followed by 2 additional courses of consolidation therapy for up to a maximum of 6 courses.

At 2-6 months following completion of chemotherapy, patients achieving adequate disease response receive vaccination consisting of recombinant tumor derived immunoglobulin idiotype with keyhole limpet hemocyanin conjugate subcutaneously (SQ) followed by sargramostim (GM-CSF) SQ, each at 2 separate sites on day 1. Patients receive GM-CSF alone on days 2-4. Vaccination repeats every 4 weeks for 4 doses, followed 3 months later by the fifth and final dose.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: Not specified

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed aggressive non-Hodgkin's lymphoma; Diffuse mixed cell; Diffuse large cell; Immunoblastic; Follicular large cell with more than 50% large cells; Mantle cell
• Non-age adjusted International Prognostic Index 2-4
• Tumor sample safely accessible by biopsy, needle aspiration, or phlebotomy; Must have adequate circulating lymphoma cells
• No CNS metastasis

--Prior/Concurrent Therapy--

• Biologic therapy: No prior biologic therapy for lymphoma
• Chemotherapy: No prior cytotoxic chemotherapy for lymphoma
• Endocrine therapy: No prior steroids for lymphoma; At least 2 months since prior nonphysiologic doses of prednisone of greater than 20 mg or equivalent; No concurrent maintenance steroids or greater than 5mg of daily prednisone or equivalent
• Radiotherapy: No prior radiotherapy for lymphoma
• Surgery: Not specified

--Patient Characteristics--

• Age: Over 18
• Performance status: Karnofsky 80-100%
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 2,500/mm3; Platelet count greater than 100,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: Bilirubin less than 2.0 mg/dL; SGOT/SGPT less than 2 times normal
• Renal: Creatinine less than 2.0 mg/dL
• Other: No other illness or condition, including innate or pharmacologic immunosuppression, that would preclude study; No other malignancy within the last 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix; HIV negative; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for 6 months after the study

California
      Stanford University Medical Center, Stanford,  California,  94305-5408,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States

Study chairs or principal investigators

Julie M. Vose,  Study Chair,  University of Nebraska   

Study ID Numbers:  CDR0000067440; UNMC-197-99; GENITOPE-9902; SUMC-9902
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  January 21, 2000
ClinicalTrials.gov Identifier:  NCT00004197
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08