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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 participants
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
Study Start Date :	November 2007
Estimated Primary Completion Date :	June 2009

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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ClinicalTrials.gov Identifier:	NCT00621036 History of Changes
Other Study ID Numbers:	CDR0000587504; SCCC-102007-035; SCCC-02F07
First Posted:	February 22, 2008
Last Update Posted:	April 2, 2010
Last Verified:	August 2008

Keywords provided by National Cancer Institute (NCI):

primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; stage IV adult T-cell leukemia/lymphoma; adult nasal type extranodal NK/T-cell lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV childhood Hodgkin lymphoma

stage IV childhood large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; stage IV mycosis fungoides/Sezary syndrome; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma; intraocular lymphoma; post-transplant lymphoproliferative disorder; cutaneous B-cell non-Hodgkin lymphoma; Waldenstrom macroglobulinemia

Additional relevant MeSH terms:

Lymphoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Lymphoproliferative Disorders; Intestinal Neoplasms; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Nervous System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases	Gastrointestinal Diseases; Intestinal Diseases; Vaccines; Methotrexate; Immunoglobulins; Antibodies; Thiotepa; Immunoglobulin Idiotypes; Immunologic Factors; Physiological Effects of Drugs; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites