Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Lymphoma

Leukemia

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphosarcoma

Germ Cells Tumors

All Drugs and Chemicals

Keyhole-limpet hemocyanin

Adjuvants, Immunologic

Immunologic Factors

Patients treated with CpG 7909 oligodeoxynucleotides (ODNs) after autologous transplantation to enhance immune reconstitution.

KLH is a foreign protein to humans, it will be used to assess the immune response to a neo-antigen given as a single injection, 1 mg subcutaneously in the arm (per MT1999-06).

keyhole limpet hemocyanin

Tetanus toxoid booster 0.5 ml intramuscularly (IM) in the opposite arm (per MT1999-06)

tetanus toxoid

Marcie Tomblyn, MD, MS

RATIONALE: Giving CpG 7909 after an autologous stem cell transplant may make a stronger immune response and prevent or delay the recurrence of cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of CpG 7909 in treating patients who have undergone autologous stem cell transplant.

OBJECTIVES:

Primary

* Determine whether CpG 7909 enhances immune function, as measured by the response to keyhole limpet hemocyanin (neo-antigen) and tetanus toxoid (memory antigen), in patients who have undergone autologous stem cell transplantation.

Secondary

* Determine if dose escalation of CpG 7909, within a range of previously tested safe doses of CpG 7909, impacts upon the primary immune readouts.

OUTLINE: This is a non-randomized, dose-escalation study of CpG 7909.

Patients receive CpG 7909 subcutaneously (SC) on days 1, 7, and 14. Patients receive keyhole limpet hemocyanin SC and tetanus toxoid SC on day 7.

Cohorts of 3-6 patients receive escalating doses of Cp6 7909 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.

Blood is collected at baseline and at approximately day 40 for immunological studies, including immunoenzyme techniques, antibody response assays, and immunophenotyping.

After completion of study treatment, patients are followed every 3 months for 1 year.

CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant

CPG 7909 Oligodeoxynucleotides (ODNS) After Autologous Transplantation to Enhance Immune Reconstitution

Masonic Cancer Center, University of Minnesota

Infections

Nervous System Diseases

Nutritional and Metabolic Diseases

Symptoms and General Pathology

Tetanus

Tetany

Communicable Diseases

Clostridium Infections

Bacterial Infections

Gram-Positive Bacterial Infections

Mycoses

Bacterial Infections and Mycoses

Gastrointestinal Agents

Vaccines

Monatide (IMS 3015)

Aluminum phosphate

Freund's Adjuvant

Intracel KLH 1000 mcg (1 mg) without adjuvant, subcutaneous Tetanus Toxoid 0.5 ml intramuscularly (this arm closed 1/2/02).

Biosyn KLH 1000 mcg (1 mg) without adjuvant, subcutaneous tetanus toxoid 0.5 ml intramuscularly (this arm closed 3/18/03).

Biosyn KLH 1000 mcg (1 mg) with Montanide ISA51 (replaced with vegetable (VG) source after 8/31/06) and subcutaneous Tetanus toxoid 0.5 ml intramuscularly.

Intracel KLH 1000 mcg (1 mg) without adjuvant, subcutaneous Tetanus Toxoid 0.5 ml intramuscularly.

Intracel KLH Vaccine

Biosyn KLH 1000 mcg (1 mg) without adjuvant, subcutaneous tetanus toxoid 0.5 ml intramuscularly.

Biosyn KLH

Emulsify the KLH with Montanide ISA-51. The KLH 1 mg vial will be reconstituted in 0.5 mL sterile water. Once solubilized, add 0.6 mL of Montanide ISA to the vial and administered contents subcutaneously.

Montanide ISA51

Tetanus Toxoid Adsorbed, Aluminum Phosphate Adsorbed, PUROGENATED® (TT), is a sterile preparation of refined tetanus toxoid for intramuscular use only.

Tetanus toxoid

Jeffrey Miller, MD

The purpose of this study is to learn how the immune system works in response to vaccines. We will give the vaccines to subjects who have cancer but have not had treatment, and to patients who have had chemotherapy or stem cell transplant. Some patients will get vaccines while they are on treatments which boost the immune system (like the immune stimulating drug interleukin-2 or IL-2). Although we have safely treated many patients with immune boosting drugs, we do not yet know if they improve the body's immune system to respond better to a vaccine. Some healthy volunteers will also be given the vaccines in order to serve as control subjects to get a good measure of the normal immune response. We will compare the patients and the healthy volunteers to study how their immune systems respond to the vaccines.

There are several different types of white cells in the blood. We are interested in immune cells in the blood called T-cells. These T-cells detect foreign substances in the body (like viruses and cancer cells). We are trying to learn more about how the body fights these foreign substances. Our goal is to develop cancer vaccines which would teach T-cells to detect and kill cancer cells better. We know that in healthy people the immune system effectively protects against recurrent virus infection. For example, that is why people only get "mono" (mononucleosis) once under normal circumstances. When the body is infected with the "mono" virus, the immune system remembers and prevents further infection. We are trying to use the immune system to prevent cancer relapse. To test this, we will give two vaccines which have been used to measure these immune responses. Blood samples will be studied from cancer patients and will be compared to similar samples from normal subjects.

Patients will receive each vaccine once only consisting of:

Arm A: Intracel KLH 1000 mcg (1 mg) without adjuvant, subcutaneous Tetanus Toxoid 0.5 ml intramuscularly (this arm closed 1/2/02).

Arm B: Biosyn KLH 1000 mcg (1 mg) without adjuvant, subcutaneous tetanus toxoid 0.5 ml intramuscularly (this arm closed 3/18/03).

Arm C: Biosyn KLH 1000 mcg (1 mg) with Montanide ISA51 (now replaced with vegetable (VG) source after 8/31/06 to increase product safety) subcutaneous Tetanus toxoid 0.5 ml intramuscularly (this arm open 3/18/03).

Subjects ineligible for tetanus may still receive KLH on this protocol. This is especially true given the national shortage of tetanus vaccines. Subjects will be eligible for tetanus when it becomes available if there has been no significant change in treatment interventions or overall health status and it is within 3 months of the KLH vaccine.

analysis of blood samples before and 4 weeks postvaccination

Vaccination With Tetanus and KLH to Assess Immune Responses.

Vaccination With Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune Responses

Glioblastoma

Brain Neoplasms

Lymphopenia

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Antineoplastic Agents

Temozolomide

Immunomodulating Agents

Patients receive CMV-ALT IV over 45-90 minutes (course 1 only) and CMV pp65-LAMP mRNA-loaded DC (CMV-DC) vaccine intradermally and administered in equal portions to each inguinal region. Vaccination repeats every 1-3 weeks for up to 3 doses in the absence of unacceptable toxicity.

Patients receive CMV-DC vaccine intradermally and administered in equal portions to each inguinal region. Vaccination repeats every 1-3 weeks for up to 3 doses in the absence of unacceptable toxicity.

Within 6 to 24 hours prior to vaccination, patients undergo skin site preparation with unpulsed DCs at the vaccination site in one inguinal region. Patients then receive indium In 111-labeled CMV-DC.

Within 6 to 24 hours prior to vaccination, patients undergo vaccination skin site preparation in the opposite inguinal region with tetanus toxoid. Patients then receive 111 In-labeled CMV-DC.

therapeutic autologous dendritic cells

therapeutic autologous lymphocytes

Katherine Peters, MD, PhD

RATIONALE: Vaccines may help the body build an effective immune response to kill cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy together with radiation therapy and chemotherapy may kill more cancer cells.

PURPOSE: This randomized phase I/II trial is studying how well vaccine therapy works in treating patients with newly diagnosed glioblastoma multiforme recovering from lymphopenia caused by temozolomide.

OBJECTIVES:

Primary

* To evaluate the feasibility and safety of vaccination with cytomegalovirus (CMV) pp65-lysosomal-associated membrane protein (LAMP) mRNA-loaded dendritic cells (DCs) during recovery from therapeutic temozolomide-induced lymphopenia with or without autologous lymphocyte transfer (ALT) in patients with newly diagnosed glioblastoma multiforme and who are seropositive or seronegative for CMV.

Secondary

* To assess humoral and cellular immune responses in these patients to CMV pp65-LAMP mRNA-loaded dendritic cell (CMV-DC) vaccine and to compare the impact of ALT and CMV seropositivity on these parameters.
* To determine if vaccination with or without ALT extends total time to progression or overall survival of these patients when compared to a recent historical cohort.
* To assess the differential ability of indium In\^111-labeled DCs to track to the inguinal lymph nodes under different skin preparative conditions.
* To assess the differential ability of \^111In-labeled DCs to track to lymph nodes on the tumor-bearing and non-tumor-bearing side of the cervical lymph nodes.
* To characterize immunologic cell infiltrate in recurrent tumors and seek evidence of antigen escape in recurrent or progressive tumors.

Patients undergo leukapheresis no more than 4 weeks after surgical resection to obtain peripheral blood lymphocytes (PBLs) for human cytomegalovirus (CMV)-autologous lymphocyte transfer (ALT) and CMV-dendritic cell (DC) generation.

Beginning 2-6 weeks after resection, patients undergo external beam radiotherapy (RT) once daily, 5 days a week, for up to 7 weeks. Beginning on day 1 of RT, patients receive oral temozolomide (TMZ) once daily for up to 49 days. Patients with progressive disease during RT, dependence on steroids above physiologic levels, intolerance to TMZ, or failure to meet cell release criteria for DCs or PBLs are removed from study.

Beginning within 2-4 weeks after completion of concurrent RT and TMZ, patients resume oral TMZ once daily on days 1-5. Treatment repeats every 4-6 weeks for up to 6 courses\* in the absence of disease progression or unacceptable toxicity. Beginning on day 19-23 of course 1, patients also receive an intradermal immunization. Patients are stratified by CMV serology status (positive vs negative) and are randomized to 1 of 2 vaccine treatment arms.

Note: \*Patients may receive additional TMZ treatment at the discretion of the patient and their treating neuro-oncologist.

* Arm I (DC vaccination plus ALT): Patients receive CMV-ALT IV over 45-90 minutes (course 1 only) and 2 x 10\^7 CMV pp65-LAMP mRNA-loaded DC (CMV-DC) vaccine intradermally and administered in equal portions to each inguinal region. Vaccination repeats every 1-3 weeks for up to 3 doses in the absence of unacceptable toxicity.
* Arm II (DC vaccination alone): Patients receive CMV-DC vaccine as in arm I. At approximately 2-6 weeks after the third vaccination, all patients undergo a second leukapheresis to obtain peripheral blood mononuclear cells for immunologic monitoring and additional DCs for continued vaccinations. Patients may undergo an additional leukapheresis if they achieve a positive immunological response to therapy or if they require additional DCs to be generated due to a prolonged progression-free survival. Leukapheresis may be performed monthly, but will likely be performed every 4 months throughout the study to generate enough DCs to continue monthly vaccinations.
* Additional cohort (GM-CSF): Patients receive CMV-DC vaccine as in arm II, except that they will also receive GM-CSF in each vaccine. Vaccines continue for a total of 10 unless tumor progression occurs. Patients in this cohort may be enrolled at any point prior to completion of adjuvant TMZ provided they meet all other eligibility criteria.

Prior to the fourth vaccination, patients in both arms and patients with disease progression determined prior to the first scheduled vaccination are stratified according to side of inguinal injection (left vs right) and vaccination skin site preparation (unpulsed DCs vs tetanus toxoid). Patients are then randomized to 1 of 2 treatment arms.

* Arm I (unpulsed DCs): Within 6 to 24 hours prior to vaccination, patients undergo skin site preparation with 1 x 10\^6 unpulsed DCs at the vaccination site in one inguinal region. Patients then receive indium In\^111-labeled CMV-DC.
* Arm II (tetanus toxoid): Within 6 to 24 hours prior to vaccination, patients undergo vaccination skin site preparation in the opposite inguinal region with tetanus toxoid. Patients then receive indium In\^111-labeled CMV-DC as in arm I.

At the time of progression, patients receive a final intradermal vaccination comprising \^111In-labeled CMV-DCs at the base of the jaw bilaterally and to the inguinal region, as a control. Gamma camera images are then taken at 24 and 48 hours after the vaccination to compare DC migration in the groin to each side of the neck injection sites and to observe migration from the neck injection sites to the deep and superficial cervical lymph nodes.

After completion of TMZ therapy, patients continue receiving DC vaccinations in the absence of disease progression (except GM-CSF cohort - total of 10 vaccinations).

Patients undergo blood sample collection periodically for immunologic studies. Samples are examined for functional CD4 and CD8 immune response of patients by cytokine fluorescent cytometry; enumeration of pp65 antigen-specific CD8+ T cells by tetramer analysis; antigen-induced T-cell proliferation; cytokine secretion and quantitative anti-pp65 antibody concentration in the serum by ELISA; and CMV pp65 quantitation in genomic DNA by reverse transcriptase-polymerase chain reaction. Patients may also undergo stereotactic biopsy or tumor resection to confirm tumor progression histologically and to assess immunologic cell infiltration and pp65 antigen escape at the tumor site by immunohistochemistry and polymerase chain reaction.

Quality of life is assessed by the self-reported Functional Assessment of Cancer Therapy-Brain questionnaire at initial leukapheresis, at the first vaccination, after the third vaccination at the time of post-vaccine leukapheresis, and then with every even-numbered vaccination thereafter. A neuropsychological assessment is also conducted prior to the first vaccine and then with every second vaccination thereafter in order to monitor for any changes in neurocognitive or affective changes.

After completion of study therapy, patients are followed periodically.

Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Anti-Tumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed Glioblastoma Multiforme During Recovery From Therapeutic Temozolomide-induced Lymphopenia

National Cancer Institute (NCI)

Gary Archer Ph.D.

Assistant Professor Neurosurgery

Digestive System Diseases

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Herbal and Botanical

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Calcium

Calcium, Dietary

Hormones

Antimetabolites

Immunosuppressive Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Cola

Folate

Vitamin B9

ALVAC-CEA-B7.1 vaccine

FOLFIRI regimen

fluorouracil

irinotecan hydrochloride

leucovorin calcium

Howard L. Kaufman, MD

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tetanus toxoid may make tumor cells more sensitive to chemotherapy and vaccine therapy.

PURPOSE: Randomized phase II trial to study the effectiveness of chemotherapy and vaccine therapy with or without tetanus toxoid compared with chemotherapy alone in treating patients who have metastatic colorectal cancer.

OBJECTIVES:

* Determine the safety of ALVAC-CEA-B7.1 vaccine and chemotherapy, with or without tetanus toxoid, vs chemotherapy alone in patients with metastatic colorectal adenocarcinoma.
* Determine whether tetanus toxoid enhances the immune response in patients treated with the vaccine and chemotherapy.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive a priming dose of tetanus toxoid. Beginning 2 weeks later, patients receive tetanus toxoid and ALVAC-CEA-B7.1 vaccine subcutaneously (SC) once weekly for 3 weeks.

Two weeks after the third vaccine administration, patients receive tetanus toxoid and ALVAC-CEA-B7.1 vaccine SC on day 1 and irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive ALVAC-CEA-B7.1 vaccine and chemotherapy as in arm I.
* Arm III: Patients receive chemotherapy as in arm I. After completion of chemotherapy, patients with partial or complete response may receive ALVAC-CEA-B7.1 vaccine SC once weekly on weeks 1-3 and 6.

PROJECTED ACCRUAL: A total of 90 patients (30 per treatment arm) will be accrued for this study.

Vaccine Therapy and Chemotherapy With or Without Tetanus Toxoid Compared With Chemotherapy Alone in Treating Patients With Metastatic Colorectal Cancer

Pilot Phase II Study of Safety and Immunogenicity of an ALVAC-CEA/B7.1 Vaccine Administered With Chemotherapy, Alone or in Combination With Tetanus Toxoid, as Compared to Chemotherapy Alone, in Patients With Metastatic Colorectal Adenocarcinoma

Herbert Irving Comprehensive Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant	NCT00369291	Germ Cell Tumor Leukemia Lymphoma Multiple Myelom...	keyhole limpet ... tetanus toxoid	18 Years -	Masonic Cancer Center, University of Minnesota
Vaccination With Tetanus and KLH to Assess Immune Responses.	NCT00000105	Cancer	Intracel KLH Va... Biosyn KLH Montanide ISA51 Tetanus toxoid	18 Years -	Masonic Cancer Center, University of Minnesota
Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT00639639	Malignant Neopl...	tetanus toxoid therapeutic aut... therapeutic aut...	18 Years -	Duke University
Vaccine Therapy and Chemotherapy With or Without Tetanus Toxoid Compared With Chemotherapy Alone in Treating Patients With Metastatic Colorectal Cancer	NCT00027833	Colorectal Canc...	ALVAC-CEA-B7.1 ... tetanus toxoid FOLFIRI regimen fluorouracil irinotecan hydr... leucovorin calc...	18 Years -	National Cancer Institute (NCI)
Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT00639639	Malignant Neopl...	tetanus toxoid therapeutic aut... therapeutic aut...	18 Years -	Duke University

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