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T Cell Immunotherapy Plus Anti-PD1 Antibody in Advanced Solid Malignancies

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ClinicalTrials.gov Identifier: NCT02757391
Recruitment Status : Not yet recruiting
First Posted : May 2, 2016
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if it is safe to deliver a CD8+T cell therapy to patients with advanced gastrointestinal cancers.

This study will use your tumor cells (either from a fresh biopsy or from leftover tissue samples) and blood to help create a T cell immune-based therapy designed specifically for you based on what the study doctor and research staff can learn about the type of mutated proteins (a type of genetic change) in the tumor.


Condition or disease Intervention/treatment Phase
Gastrointestinal Cancer Metastatic Drug: Standard Chemotherapy Drug: Cyclophosphamide Biological: Adoptive T Cell Infusion Drug: IL-2 Drug: Pembrolizumab Behavioral: Phone Calls Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Feasibility and Safety of Personalized Autologous Cluster of Differentiation 8 (CD8+) T Cell Therapy Plus Anti-PD1Antibody in Advanced Solid Malignancies
Anticipated Study Start Date : April 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Adoptive T Cells + Pembrolizumab

Participant has least 1 type of chemotherapy after enrollment in this study, but before T cell dose. Chemotherapy used at the discretion of treating physician.

On Day -2, participants receive Cyclophosphamide 300 mg/m2 by vein over 30 minutes 48 to 72 hours prior to T cell infusion as an outpatient procedure.

On Day 0 participants receive adoptive t cell infusion. A target of at 20 x 10^9 T cells / m2 infused.

On Day 0 to Day +13, participants receive low-dose IL-2 250,000 units/m2 subcutaneously every 12 hours within 6 hours of T cell infusion and continue for a total of 14 days (28 doses).

On Day +1 and Weeks 3, 6, 9, 12, and 15, Pembrolizumab 200 mg by vein.

Participant called twice by study staff in the 6 months after they are off the study.

Drug: Standard Chemotherapy
Participant has least 1 type of chemotherapy after enrollment in this study, but before T cell dose. Chemotherapy used at the discretion of treating physician.
Drug: Cyclophosphamide
300 mg/m2 by vein on Day -2, 48 to 72 hours prior to T cell infusion.
Other Names:
  • Cytoxan
  • Neosar
Biological: Adoptive T Cell Infusion
On Day 0 participants receive adoptive t cell infusion. A target of at 20 x 10^9 T cells / m2 infused.
Drug: IL-2
250,000 units/m2 subcutaneously On Day 0 to Day +13 every 12 hours within 6 hours of T cell infusion and continue for a total of 14 days (28 doses).
Other Names:
  • Aldesleukin
  • Interleukin-2
  • Proleukin
Drug: Pembrolizumab
200 mg by vein on Day +1 and Weeks 3, 6, 9, 12, and 15,
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475
Behavioral: Phone Calls
Participant called twice by study staff in the 6 months after they are off the study.



Primary Outcome Measures :
  1. Toxicity of Personalized Adoptive T Cell Therapy in Participants with Advanced Gastrointestinal Malignancies [ Time Frame: 24 weeks ]
    Toxicity defined as proportion of treated patients experiencing at least one grade 3/4 non-hematologic toxicity or one grade 4 hematologic toxicity attributable to therapy at any point on study per CTCAE v4.0.


Secondary Outcome Measures :
  1. Persistence of Immune Response After Personalized Adoptive T Cell Therapy in Participants with Advanced Gastrointestinal Malignancies [ Time Frame: 12 weeks after T cell infusion ]
    Persistence of an immune response as defined by level of tetramer positive T cell population over time after T cell infusion. Response criteria according to RECIST 1.1.

  2. Persistence of Immune Response After Personalized Adoptive T Cell Therapy in Participants with Advanced Gastrointestinal Malignancies [ Time Frame: 12 weeks after T cell infusion ]
    Persistence of an immune response as defined by T cell IFN-γ release in response to selected personalized peptide antigens. Response criteria according to RECIST 1.1.

  3. Persistence of Immune Response After Personalized Adoptive T Cell Therapy in Participants with Advanced Gastrointestinal Malignancies [ Time Frame: 12 weeks after T cell infusion ]
    Persistence of an immune response as defined by levels of Intracellular cytokine staining of T cells by flow cytometry in response to stimulation with personalized peptide antigens. Response criteria according to RECIST 1.1.

  4. Persistence of Immune Response After Personalized Adoptive T Cell Therapy in Participants with Advanced Gastrointestinal Malignancies [ Time Frame: 12 weeks after T cell infusion ]
    Persistence of an immune response as defined by detection of antigen spreading. Response criteria according to RECIST 1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma, cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of metastatic disease.
  2. Male or female subjects greater than or equal to 18 years of age.
  3. ECOG/ Zubrod performance status of 0 or 1.
  4. 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 spermicide. Abstinence is also an acceptable form of birth control.
  5. 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.
  6. Willing and able to give informed consent.
  7. Adequate vein access: consider PICC or other central line.
  8. 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.
  9. Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest.
  10. Toxicity related to prior therapy must either have returned to </= grade 1, baseline, or been deemed irreversible.
  11. ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2.
  12. Bi-dimensionally measurable disease by radiographic imaging (CT scan) that represents at least one measurable lesion per RECIST v1.1.
  13. At least 4 Weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery.
  14. Toxicity related to prior therapy must either have returned to less than or equal to grade 1, baseline, or been deemed irreversible.
  15. 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 Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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
  8. 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
  9. 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
  10. 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.
  11. Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
  12. 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.
  13. Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any anti-PD-1 dose.
  14. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02757391


Contacts
Contact: Cassian Yee, MD 713-563-3750 CR_Study_Registration@mdanderson.org
Contact: Clinical Research Operations MD Anderson Cancer Center 713-792-7734 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Cassian Yee, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02757391     History of Changes
Other Study ID Numbers: 2015-0152
NCI-2016-01058 ( Registry Identifier: NCI CTRP )
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: January 24, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Advanced gastrointestinal malignancies
Metastatic gastrointestinal tumor
Adoptive T cell infusion
Cyclophosphamide
Cytoxan
Neosar
IL-2
Aldesleukin
Interleukin-2
Proleukin
Pembrolizumab
Keytruda
MK-3475
SCH-900475
Phone calls

Additional relevant MeSH terms:
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Cyclophosphamide
Pembrolizumab
Aldesleukin
Interleukin-2
Antibodies
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents