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

Sponsored by:	Simmons Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00621036

Purpose

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	Intervention	Phase
Lymphoma	Drug: autologous immunoglobulin idiotype-KLH conjugate vaccine Drug: methotrexate Drug: sargramostim Drug: thiotepa Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Methotrexate Thiotepa Sargramostim Granulocyte-macrophage colony-stimulating factor Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) immune response rate in the CSF [ Designated as safety issue: No ]
Safety and tolerability [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free survival (PFS) [ Designated as safety issue: No ]
Time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine [ Designated as safety issue: No ]
Correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival [ Designated as safety issue: No ]
Kinetics of humoral immune response development [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	November 2007
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621036

Locations

United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Recruiting
Dallas, Texas, United States, 75390
Contact: Clinical Trials Office - Simmons Comprehensive Cancer Center a 866-460-4673; 214-648-7097

Sponsors and Collaborators

Simmons Cancer Center

Investigators

Principal Investigator:

Elizabeth Maher, MD, PhD

Simmons Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000587504, SCCC-102007-035, SCCC-02F07
Study First Received:	February 21, 2008
Last Updated:	September 22, 2008
ClinicalTrials.gov Identifier:	NCT00621036
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

primary central nervous system lymphoma

Study placed in the following topic categories:

Folic Acid
Lymphatic Diseases
Antibodies
Immunoproliferative Disorders
Immunoglobulin Idiotypes
Methotrexate

Lymphoproliferative Disorders
Lymphoma
Immunoglobulins
Thiotepa
Central nervous system lymphoma, primary

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents

Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Abortifacient Agents
Antirheumatic Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009