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

NCT ID: NCT00621036

Last Updated: 2018-11-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-19
• Study Completion Date: 2008-12-08

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.

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.

Conditions

Brain and Central Nervous System Tumors; Lymphoma; Lymphoproliferative Disorder; Small Intestine Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

methotrexate IV once every 2 weeks

Group Type: EXPERIMENTAL

autologous immunoglobulin idiotype-KLH conjugate vaccine

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

methotrexate

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Interventions

autologous immunoglobulin idiotype-KLH conjugate vaccine

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

methotrexate

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Maher, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Simmons Cancer Center

Locations

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Countries

United States

Other Identifiers

SCCC-102007-035

Identifier Type: -

Identifier Source: secondary_id

CDR0000587504

Identifier Type: REGISTRY

Identifier Source: secondary_id

SCCC-02F07

Identifier Type: -

Identifier Source: org_study_id