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Sponsored by: |
University of Pittsburgh |
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Information provided by: | University of Pittsburgh |
ClinicalTrials.gov Identifier: | NCT00819806 |
Subjects will receive immunizations every other week for 8 immunizations prior to clinical and immunological evaluations. Patients will then receive immunizations every month up to one year. Cyclophosphamide will be administered intravenously 3 days prior to the first immunization, 3rd, 5th, 7th, 9th, and subsequent monthly immunizations. Women and men >= 18 years of age with refractory metastatic malignancies that express NY-ESO-1 by RT-PCR or immunohistochemistry. Alternatively, patients may be elected on the basis of serum anti-NY-ESO-!-antibodies as detected by ELISA.
Primary Objective: To evaluate the toxicity profile of the regimens described in Section 1.6.
Secondary Objective: To detect and quantitate immune responses induced by the proposed peptide vaccine or protein vaccine in association with CpG 7909 and cyclophosphamide. This endpoint will be assessed by an IFN-y ELISPOT assay of NY-ESO-1-specific tumor-reactive CD8 + T cells. We also will look for NY-ESO-1 tetramer CD8+ T cells, Delayed-type Hypersensitivity (DTH), and NY-ESO-1-specific CD4+ T cell responses with ELISPOT assays and cytokine-release-assays.
Tertiary Objectives: To evaluate tumor response in terms of clinical tumor regression and progression-free interval. To evaluate the survival of patients treated with the regimens described in Section 1.6.
The first 3 patients will be assigned treatment A. All three patients will be treated and observed for one month. If no DLTs are observed in the first 3 patients, accrual to arm A will be put on hold and accrual will continue with Arm B. However, if 1 DLT is observed in Arm A, up to 3 additional patients will be treated on Arm A, until either 2 DLTs have been observed, or 6 patients have been treated with just 1 DLT among them. If 2 DLTs are observed in Arm A, the study will terminate and all treatments will be deemed intolerable. The same principles apply to the cohorts treated on B-E: if the number of DLTs (after one month of treatment) is zero, accrual proceeds to the next treatment group; if it is 1, accrual continues with the same treatment for up to 3 additional patients; if it is 2, no patients will be treated on the remaining treatment arms.
Condition | Intervention | Phase |
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NY-ESO-1-Expressing Tumors |
Biological: Vaccine only Biological: Vaccine + cyclophosphamide |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study |
Official Title: | Phase I Study of Vaccination With CpG 7909 and Montanide ISA 720 With or Without Cyclophosphamide in Combination Either With NY-ESO-1-Derived Peptides or the NY-ESO-1 Protein in Patients With NY-ESO-1-Expressing Tumors |
Estimated Enrollment: | 42 |
Study Start Date: | January 2009 |
Estimated Study Completion Date: | January 2015 |
Estimated Primary Completion Date: | January 2015 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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A: Experimental
PF-3512676, and three MHC class I Montanide ISA 720 VG and the peptides NY-ESO-1 157-165V, NY-ESO-1 53-62 and NY-ESO-1 94-102 will be administered in three separate subcutaneous (under the skin) injections.
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Biological: Vaccine only
PF-3512676, Montanide ISA 720 VG and MHC class I peptides from NY-ESO-1 (NY-ESO-1 157-165V, NY-ESO-1 53-62 (MPS-190) and NY-ESO-1 94-102) in three subcutaneous injections (i.e., 1mg of PF-3512676 at 15mg/ml and 50 μg of each peptide (2mg/ml) for each of the three injections + Montanide ISA 720 VG + saline). The final volume of immunization will be 4.5 ml administered as 3 separate 1.5 ml subcutaneous injections. The remaining 1.5 ml will be used for sterility testing. Each injection will be done in the vicinity of the nodal drainage of one extremity.
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B: Experimental
This vaccine injection contains all the same components of Arm A and will also be administered in 3 separate subcutaneous injections. However, 3 days prior to your 1st, 3rd, 5th, 7th, 9th and subsequent monthly vaccinations, you will have low-dose cyclophosphamide administered intravenously (through a vein in your arm). Cyclophosphamide is an agent that is thought to increase the anti-tumor response of vaccines.
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Biological: Vaccine + cyclophosphamide
PF-3512676, Montanide ISA 720 VG and three MHC class I-restricted epitopes from NY-ESO-1 (NY-ESO-1 157-165V, NY-ESO-1 53-62 (MPS-190) and NY-ESO-1 94-102) and cyclophosphamide. The vaccine preparation is identical to arm A. Each injection will be done in the vicinity of the nodal drainage of one extremity. Each will consist of 1.5 ml of product. Low-dose cyclophosphamide (300mg/m2) will be given IV, monthly, 3 days prior to the first, 3rd, 5th, 7th, 9th, and subsequent monthly immunizations.
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C: Experimental
PF-3512676, Montanide ISA 720 VG and the peptides NY-ESO-1 157-165V, NY-ESO-1 53-62 and NY-ESO-1 94-102, NY-ESO-1 87-111, NY-ESO-1 119-143 and NY-ESO-1 157-170 will be administered in three separate subcutaneous injections.
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Biological: Vaccine only
PF-3512676, Montanide ISA 720 VG and three MHC class I epitopes (NY-ESO-1 157-165V, NY-ESO-1 53-62 and NY-ESO-1 94-102) and three MHC class II epitopes (NY-ESO-1 87-111, NY-ESO-1 119-143 and NY-ESO-157-170) in three subcutaneous injections (i.e., 1mg of PF-3512676 at 15mg/ml and 50 μg of each peptide (2mg/ml) for each of the three injections + Montanide ISA 720 VG + saline). The final volume of immunization will be 4.5 ml administered as 3 separate 1.5 ml subcutaneous injections. Each injection will be done in the vicinity of the nodal drainage of one extremity. Each will consist of 1.5 ml of product.
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D: Experimental
This vaccine injection contains all the same components of Arm C and will also be administered in 3 separate subcutaneous injections. However, 3 days prior to your 1st, 3rd, 5th, 7th, 9th and subsequent monthly vaccinations, you will have low-dose cyclophosphamide administered intravenously (through a vein in your arm).
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Biological: Vaccine + cyclophosphamide
PF-3512676, Montanide ISA 720 VG and three MHC class I epitopes (NY-ESO-1 157-165V, NY-ESO-1 53-62 and NY-ESO-1 94-102), three MHC class II epitopes (NY-ESO-1 87-111, NY-ESO-1 119-143 and NY-ESO-157-170) and cyclophosphamide. The vaccine preparation is identical to arm C. Low-dose cyclophosphamide (300mg/m2) IV will be given IV, monthly, 3 days prior to the first, 3rd, 5th, 7th, 9th, and subsequent monthly immunizations.
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E: Experimental
PF-3512676, Montanide ISA 720 VG and the NY-ESO-1 protein will be administered in three separate subcutaneous injections.
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Biological: Vaccine only
PF-3512676, Montanide ISA 720 VG and the NY-ESO-1 protein in three subcutaneous injection (i.e. 3 mg of PF-3512676 or 300 μl of PF-3512676 at 10mg/ml, 300 μg or 900 μl of protein NY-ESO-1 at 0.35 mg/ml + Montanide ISA 720 VG). The final volume of immunization will be 4.5 ml administered as 3 separate 1.5 ml SC injections. Each injection will be done in the vicinity of the nodal drainage of one extremity. Each will consist of 1.5 ml of product.
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F: Experimental
This vaccine injection contains all the same components of Arm E and will also be administered in 3 separate subcutaneous injections. However, 3 days prior to your 1st, 3rd, 5th, 7th, 9th and subsequent monthly vaccinations, you will have low-dose cyclophosphamide administered intravenously (through a vein in your arm).
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Biological: Vaccine + cyclophosphamide
PF-3512676, Montanide ISA 720 VG and the NY-ESO-1 protein in three subcutaneous injections and cyclophosphamide. The vaccine preparation is identical to arm E. Low-dose cyclophosphamide (300mg/m2) will be given IV, monthly, 3 days prior to the first, 3rd, 5th, 7th, 9th, and subsequent monthly immunizations.
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Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Responsible Party: | University of Pittsburgh Cancer Institute ( Hassane Zarour, MD ) |
Study ID Numbers: | 05-140, 1R01CA112198-01 |
Study First Received: | January 7, 2009 |
Last Updated: | January 7, 2009 |
ClinicalTrials.gov Identifier: | NCT00819806 |
Health Authority: | United States: Food and Drug Administration |
Mannitol Cyclophosphamide |
Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Diuretics, Osmotic Physiological Effects of Drugs Diuretics Cardiovascular Agents Immunosuppressive Agents |
Pharmacologic Actions Natriuretic Agents Therapeutic Uses Myeloablative Agonists Antineoplastic Agents, Alkylating Antirheumatic Agents Alkylating Agents |