- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02757391
CD8+ T Cell Therapy and Pembrolizumab in Treating Patients With Metastatic Gastrointestinal Tumors
Pilot Study of Feasibility and Safety of Personalized Autologous CD8+ T Cell Therapy Plus Anti-PD1 Antibody in Advanced Solid Malignancies
Study Overview
Status
Conditions
- Metastatic Pancreatic Adenocarcinoma
- Stage IV Pancreatic Cancer AJCC v6 and v7
- Stage IV Colorectal Cancer AJCC v7
- Stage IVA Colorectal Cancer AJCC v7
- Stage IVB Colorectal Cancer AJCC v7
- Colorectal Adenocarcinoma
- Metastatic Colorectal Carcinoma
- Metastatic Cholangiocarcinoma
- Metastatic Digestive System Carcinoma
- Metastatic Esophageal Carcinoma
- Metastatic Gastric Carcinoma
- Stage IV Esophageal Cancer AJCC v7
- Stage IV Gastric Cancer AJCC v7
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion:
- Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma, cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of metastatic disease.
- Male or female subjects greater than or equal to 18 years of age.
- ECOG/ Zubrod performance status of 0 or 1.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for at least 8 weeks after pembrolizumab is stopped. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Acceptable forms of birth control include condom, diaphragm, hormonal, IUD, or sponge plus spermacide. Abstinence is also an acceptable form of birth control.
- Men must be willing and able to use an acceptable method of birth control, during and for at least 3 months after completion of the study, if their sexual partners are WOCBP.
- Willing and able to give informed consent.
- Adequate vein access: consider PICC or other central line.
- Patients must have adequate tissue (fresh or frozen) available or planned removal of adequate tissue for analysis. At least 250mg of tumor are needed for peptide elution. There is no specific time limit on how long the tissue can remain frozen prior to use. The tissue will be collected and analyzed under Lab protocol PA15-0176.
- Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest.
- Toxicity related to prior therapy must either have returned to </= grade 1, baseline, or been deemed irreversible.
- ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2.
- Bi-dimensionally measurable disease by radiographic imaging (CT scan) that represents at least one measurable lesion per RECIST v1.1.
- At least 4 Weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery.
- Toxicity related to prior therapy must either have returned to less than or equal to grade 1, baseline, or been deemed irreversible.
- Subjects must have received at least one line of chemotherapy prior to receiving adoptive T cell therapy and should have exhausted standard of care systemic therapy options. The decision to implement the T cell therapy will be at the discretion of the treating physician. The timing and total exposure to chemotherapy will depend on the tumor type in question (more systemic options for breast cancer; fewer for gastric cancer, for example). Due to the heterogeneity of tumors being treated in this protocol, the discretion of the treating physician in terms of timing of immunotherapy will be critical.
Exclusion:
- EXCLUSION FOR ENROLLMENT: Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ of the cervix.
- Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
- Significant cardiovascular abnormalities as defined by any one of the following: 1. Congestive heart failure NYHA classes II-IV. Patients with asymptomatic class I CHF may participate in conjunction with a Cardiology consultation. 2. Clinically significant hypotension. 3. Symptoms of coronary artery disease. 4. Presence of arrhythmias in EKG requiring drug therapy.
- Active and untreated central nervous system (CNS) metastases (including metastasis identified during screening MRI or contrast CT). Patients with asymptomatic, treated metastases may be eligible if their lesion(s) have demonstrated stability over 2 months.
- Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
- Inadequate organ function at enrollment defined by: WBC less than or equal to 2000/uL. Hct less than or equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or equal to 1000. Platelets less than or equal to 75,000. Creatinine greater than or equal to 1.5 x ULN OR creatinine clearance >50 ml/min/1.73m2 for patients with creatinine levels above institutional normal limits. AST/ALT greater than or equal to 2.5 x ULN. Bilirubin greater than or equal to 2.0 x ULN
- Positive screening tests for HIV, Hep B, and Hep C. If positive results are not indicative of true active or chronic infection, the patient can be treated
- EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL. Hct less than or equal to 24% or Hgb less than or equal to 8 g/dL. ANC less than or equal to 1000. Platelets less than or equal to 75,000. Creatinine greater than or equal to 1.5 x ULN OR creatinine clearance >50 ml/min/1.73m2 for patients with creatinine levels above institutional normal limits. AST/ALT greater than or equal to 2.5 x ULN. Bilirubin greater than or equal to 2.0 x ULN
- Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
- Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
- Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any anti-PD-1 dose.
- After the T cell infusion, patients may not be on any other treatments for their cancer aside from those included in the treatment section of the protocol.
- Coagulation ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or a PTT is within therapeutic range of intended use of anticoagulants.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (CD8 +T cell therapy, 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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Undergo CD8 +T cell therapy
Other Names:
Given SC
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
Time Frame: 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.
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Up to 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Persistence of an immune response defined by level of tetramer positive T cell population over time after T cell infusion
Time Frame: Up to 24 weeks
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Up to 24 weeks
|
|
Persistence of an immune response defined by T cell interferon gamma release in response to selected personalized peptide antigens
Time Frame: Up to 24 weeks
|
Up to 24 weeks
|
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Persistence of an immune response defined by levels of intracellular cytokine staining of T cells in response to stimulation with personalized peptide antigens
Time Frame: Up to 24 weeks
|
Up to 24 weeks
|
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Persistence of an immune response defined by detection of antigen spreading
Time Frame: Up to 24 weeks
|
Up to 24 weeks
|
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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
Time Frame: At 12 weeks post infusion
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At 12 weeks post infusion
|
|
Time to progression
Time Frame: Up to 24 weeks
|
Up to 24 weeks
|
|
Response rate (CR + PR)
Time Frame: Up to 24 weeks
|
The response rate will be evaluated using a Simon optimal two-stage design.
|
Up to 24 weeks
|
Overall survival
Time Frame: Up to 24 weeks
|
Up to 24 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Overman, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Head and Neck Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Esophageal Diseases
- Stomach Neoplasms
- Carcinoma
- Colorectal Neoplasms
- Adenocarcinoma
- Cholangiocarcinoma
- Esophageal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Aldesleukin
- Cyclophosphamide
- Pembrolizumab
- Immunologic Factors
- Interleukin-2
Other Study ID Numbers
- 2015-0152 (Other Identifier: M D Anderson Cancer Center)
- NCI-2016-01058 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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