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

Primary Purpose

Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
autologous immunoglobulin idiotype-KLH conjugate vaccine
sargramostim
methotrexate
thiotepa
radiation therapy
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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 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, Waldenström macroglobulinemia, small intestine lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

methotrexate IV once every 2 weeks

Arm Description

Outcomes

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

Full Information

First Posted
February 21, 2008
Last Updated
November 21, 2018
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00621036
Brief Title
Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Withdrawn
Why Stopped
MyVax did not meet its primary endpoints
Study Start Date
October 19, 2007 (Actual)
Primary Completion Date
December 8, 2008 (Actual)
Study Completion Date
December 8, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer
Keywords
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 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, Waldenström macroglobulinemia, small intestine lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
methotrexate IV once every 2 weeks
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
autologous immunoglobulin idiotype-KLH conjugate vaccine
Intervention Type
Biological
Intervention Name(s)
sargramostim
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Anti-idiotype (Id) and anti-keyhole limpet hemocyanin (KLH) immune response rate in the CSF
Title
Safety and tolerability
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Title
Time to receipt of first subsequent anti-lymphoma therapy after initiating immunization with the Id-KLH conjugate vaccine
Title
Correlation of anti-Id immune response in the CSF and/or serum with PFS and overall survival
Title
Kinetics of humoral immune response development

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth Maher, MD, PhD
Organizational Affiliation
Simmons Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

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

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