Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma

The University of Texas System (UT)

Status and phase

Withdrawn

Phase 2

Conditions

Brain and Central Nervous System Tumors

Lymphoproliferative Disorder

Lymphoma

Small Intestine Cancer

Treatments

Drug: thiotepa

Radiation: radiation therapy

Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine

Biological: sargramostim

Drug: methotrexate

Study type

Interventional

Funder types

Other

Identifiers

NCT00621036

SCCC-02F07

SCCC-102007-035

CDR0000587504 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's cancer proteins may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy together with GM-CSF may make a stronger immune response and kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving vaccine therapy together with GM-CSF works in treating patients with CNS lymphoma.

Full description

OBJECTIVES:

Primary

To determine the proportion of patients with CNS lymphoma who develop anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) humoral immune responses in the serum and/or CSF following patient-specific immunotherapy comprising recombinant tumor-derived immunoglobulin Id-KLH conjugate vaccine and sargramostim (GM-CSF).
To assess the safety and tolerability of this regimen in these patients.

Secondary

To evaluate the progression-free survival (PFS) of patients treated with this regimen.
To determine the time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine.
To assess the correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival.

Tertiary

To evaluate the kinetics of humoral immune response development in patients treated with this regimen.

OUTLINE:

Pre-immunotherapy: Patients submit a tumor sample for manufacturing of the idiotype (Id)-keyhole limpet hemocyanin (KLH) conjugate vaccine and undergo placement of an Ommaya reservoir. Patients then receive induction therapy comprising methotrexate IV once every 2 weeks until a maximum radiographic response is achieved, as assessed by MRI of the brain. Patients then receive methotrexate IV once a month for 6 months. Patients with leptomeningeal or CSF involvement also receive intraventricular thiotepa twice a week until the CSF is clear on three evaluations and then once a week until the CSF is clear on four evaluations. Patients under 55 years of age also undergo whole brain radiotherapy (or craniospinal radiotherapy when extensive leptomeningeal disease is present). Patients who achieve a stable response to induction therapy proceed to immunotherapy.
Immunotherapy: Patients receive recombinant tumor-derived immunoglobulin Id-KLH conjugate vaccine subcutaneously (SC) on day 1 of weeks 0, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76. Patients also receive sargramostim (GM-CSF) SC on days 1-4 of the same weeks as the Id-KLH conjugate vaccine.

After completion of therapy, patients are followed periodically for up to 2 years.

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or CSF cytologically confirmed CNS lymphoma with any of the following clinical histories:
- Primary CNS lymphoma at initial diagnosis
- Primary CNS lymphoma at relapse
- Systemic lymphoma with CNS disease at initial diagnosis or at relapse
Adequate fresh tissue or cell pellet available for analysis by Genitope Corporation to determine adequacy for idiotype (Id) manufacturing
Tumor must express both functional light and heavy chain genes
No tumors known or found to be surface immunoglobulin negative
Not in leukemic phase (i.e., > 5,000/mm³ circulating tumor cells)

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%
WBC ≥ 1,500/mm³
Platelet count ≥ 75,000/mm³
Hemoglobin ≥ 10 g/dL
Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's disease)
Creatinine ≤ 1.5 times ULN
Able to undergo placement of an Ommaya reservoir
Able to receive induction therapy (chemotherapy with or without brain radiotherapy) with intent to induce remission
Speaks English or Spanish
No other malignancy within the past 3 years, except adequately treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ
Not pregnant or nursing
No immunosuppressive viral infections as evidenced by HIV antibody or antigen, hepatitis B antigen, or hepatitis C antibody or antigen positivity
No history of autoimmune disease that required treatment within the past 5 years, including previously treated autoimmune hemolytic anemia or immune thrombocytopenia

PRIOR CONCURRENT THERAPY:

More than 30 days since prior and no concurrent participation in another therapeutic clinical trial
More than 2 weeks since prior steroids
No concurrent immunosuppressives, including corticosteroids
- Transient use of optical or nasal steroid solutions is allowed
No other concurrent anticancer therapy or therapy for non-Hodgkin lymphoma