CD8+ T Cell Therapy and Pembrolizumab in Treating Patients With Metastatic Gastrointestinal Tumors
- Conditions
- Colorectal AdenocarcinomaMetastatic Gastric CarcinomaMetastatic CholangiocarcinomaMetastatic Esophageal CarcinomaMetastatic Pancreatic AdenocarcinomaStage IV Gastric Cancer AJCC v7Stage IV Pancreatic Cancer AJCC v6 and v7Stage IV Esophageal Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Metastatic Colorectal Carcinoma
- Interventions
- Biological: Adoptive ImmunotherapyBiological: AldesleukinDrug: CyclophosphamideOther: Laboratory Biomarker AnalysisBiological: Pembrolizumab
- Registration Number
- NCT02757391
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T cells in treating patients with gastrointestinal tumors that have spread to other places in the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab may work better in treating patients with gastrointestinal tumors.
- Detailed Description
PRIMARY OBJECTIVES:
I. Assess the safety of using a personalized adoptive T cell therapy in patients with advanced gastrointestinal malignancies.
SECONDARY OBJECTIVES:
I. Assess the persistence of an immune response after T cell infusion. II. Determine the clinical benefit of adoptive T cell therapy in advanced gastrointestinal cancers.
OUTLINE:
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide intravenously (IV) over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
After completion of study treatment, patients are followed up for 24 weeks.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (CD8 +T cell therapy, pembrolizumab) Laboratory Biomarker Analysis Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15. Treatment (CD8 +T cell therapy, pembrolizumab) Aldesleukin Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15. Treatment (CD8 +T cell therapy, pembrolizumab) Adoptive Immunotherapy Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15. Treatment (CD8 +T cell therapy, pembrolizumab) Cyclophosphamide Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15. Treatment (CD8 +T cell therapy, pembrolizumab) Pembrolizumab Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide IV over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on day 0 and receive aldesleukin SC BID on days 1-14. Beginning on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over 30-60 minutes on weeks 3, 6, 12, and 15.
- Primary Outcome Measures
Name Time Method Incidence of toxicity defined as grade 3 or 4 non-hematologic or grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 4.0 Up to 24 weeks Will monitor toxicity of the personalized vaccines in using cohorts of size of 5, starting from the 1st patient using the Bayesian approach of Thall, Simon, Estey.
- Secondary Outcome Measures
Name Time Method Persistence of an immune response defined by T cell interferon gamma release in response to selected personalized peptide antigens Up to 24 weeks Persistence of an immune response defined by levels of intracellular cytokine staining of T cells in response to stimulation with personalized peptide antigens Up to 24 weeks Persistence of an immune response defined by detection of antigen spreading Up to 24 weeks Time to progression Up to 24 weeks Persistence of an immune response defined by level of tetramer positive T cell population over time after T cell infusion Up to 24 weeks Proportion of patients who have received T cell infusion that is alive and progression free (complete response [CR] + partial response [PR] + stable disease) defined based on response criteria according to Response Evaluation Criteria in Solid Tumors 1.1 At 12 weeks post infusion Response rate (CR + PR) Up to 24 weeks The response rate will be evaluated using a Simon optimal two-stage design.
Overall survival Up to 24 weeks
Trial Locations
- Locations (1)
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States