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

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00621036

Collaborator

(none)

Enrollment

Location

Arm

13.7

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma Lymphoproliferative Disorder Small Intestine Cancer	Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine Biological: sargramostim Drug: methotrexate Drug: thiotepa Radiation: radiation therapy	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of Patient-Specific Immunotherapy, Recombinant Idiotype Conjugated to KLH (Id-KLH) and Administered With GM-CSF, in Patients With CNS Lymphoma

Actual Study Start Date :

Oct 19, 2007

Actual Primary Completion Date :

Dec 8, 2008

Actual Study Completion Date :

Dec 8, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: methotrexate IV once every 2 weeks	Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine Biological: sargramostim Drug: methotrexate Drug: thiotepa Radiation: radiation therapy

Arm

Intervention/Treatment

Experimental: methotrexate IV once every 2 weeks

Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine

Biological: sargramostim

Drug: methotrexate

Drug: thiotepa

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) immune response rate in the CSF []
Safety and tolerability []

Secondary Outcome Measures

Progression-free survival (PFS) []
Time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine []
Correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival []
Kinetics of humoral immune response development []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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