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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00621036
• Other study ID #: SCCC-02F07
• Secondary ID: SCCC-102007-035C
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 19, 2007
• Est. completion date: December 8, 2008

Study information

• Verified date: November 2018
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 8, 2008
• Est. primary completion date: December 8, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Intestinal Neoplasms
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Nervous System Neoplasms
• Small Intestine Cancer

Intervention

Biological:
• autologous immunoglobulin idiotype-KLH conjugate vaccine

• sargramostim

Drug:
• methotrexate

• thiotepa

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) immune response rate in the CSF
Primary	Safety and tolerability
Secondary	Progression-free survival (PFS)
Secondary	Time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine
Secondary	Correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival
Secondary	Kinetics of humoral immune response development