Phase II/Pilot Study of 2nd Generation Anti-CEA Designer T Cells in Adenocarcinomas

NCT01723306 | Suspended Phase 2 DMC

• 1 other identifier: 306-04
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remis-sions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveillance" has manifestly failed in every cancer that is clinically apparent. It is the goal of these studies to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. This extends the approach of Anderson, Rosenberg and co-workers to introduce or augment expression of genes in patients' T cells in a therapeutic setting. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an effective, self-sustaining immune response. It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA) which is predominantly expressed on tumors of the colon and rectum, breast, pancreas and other sites.

Conditions

Metastatic Cancers

Keywords

T cells; gene transfer; immunotherapy; metastatic cancers; lung cancer; gastric cancer; colorectal cancer; solid tumors

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Monitoring of CEA levels, pre and post infusion of T cells. Monitoring of CT and PET scans pre and post infusion.

  24 months

Secondary Outcomes (1)

• Safety

  24 months

Study Arms (1)

2nd Generation Designer T Cells

EXPERIMENTAL

All participants will receive gene modified T cells, with concomitant IL2 for 30 days post infusion.

Genetic: Gene Modified T Cells

Interventions

Gene Modified T Cells GENETIC

Subjects will undergo T cell leukopheresis. The collected T cells will be genetically modified, and then re-infused peripherally. IL2 will be given concomitantly for 30 days post modified T cell infusion via CADD pump.

Also known as: 2nd Generation Designer T Cells

2nd Generation Designer T Cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed diagnosis of CEA-expressing adenocarcinoma. Patient may have measurable tumor by physical examination or by radiologic studies, and/or evaluable disease, including bone lesions. Soluble CEA is not acceptable as the sole measure of disease, although it may be followed in addition to measurable or other evaluable disease.
• Tumor must be CEA-expressing as demonstrated by elevated serum CEA levels(\>10 ng/ml). Preference will be given to patients with CEA \>100 ng/mL to increase the sensitivity of CEA as a measure of the tumor response.
• Where preserved tumor tissue is available, direct immuno¬histochemical staining of tumor is obtained to demonstrate CEA expression on tumor cells.
• Patient must be at least 18 years of age.
• Patient able to understand and sign informed consent.
• Patient with a life expectancy of greater than four months.
• Patient failed standard potentially curative therapy.
• Patient with performance status of 0 to 1 (ECOG).
• Patient with adequate organ function as defined by:
• ANC 1.0, platelets 50,000, Hgb 8.0; patient may be transfused to achieve Hgb 8.0 to satisfy enrollment criteria, or as otherwise indicated by symptoms for Hgb \>8.0.
• Creatinine 1.5mg/dl or creatinine clearance 60cc/min.
• Direct bilirubin 1.5 mg/dl.
• No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias, including atrial fibrillation/atrial flutter, evidence of prior myocardial infarction by history or by EKG.
• A normal cardiac stress test for inducible ischemia or arrhythmia within 12 weeks prior to enrollment for all patients over 50 years old or those with abnormal EKG or any history or symptoms suggestive of cardiac disease.
• \-- No serious, symptomatic obstructive or emphysematous lung disease, or asthma requiring intravenous medications within the past 12 months; no serious lung disease associated with dyspnea at normal activity levels grade III) or at rest (grade IV), due to any cause (including cancer metastases and pleural effusions). The patient will be ineligible if PFTs show an FEV1 \<1.3 liters or a DLCO \<50% within 12 weeks of study entry.

You may not qualify if:

• Female patients of childbearing age will be tested for pregnancy; pregnant patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol of human sperm and the need to practice birth control.
• Patients with serious or unstable renal, hepatic, pulmonary, cardio¬vascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded, as outlined in section 5.2.8.
• Patients with active clinical disease caused by CMV, hepatitis B or C, HIV or tuberculosis will be excluded from the study.
• Patients who have had cytotoxic and/or radiation therapy in the four weeks prior to entry into the trial will be excluded.
• Patients with other concurrent malignancies will be excluded.
• Patients requiring systemic steroids will be excluded.
• Patients previously treated with investigational agents will be excluded

Sponsors & Collaborators

• Roger Williams Medical Center: lead

Study Sites (1)

Roger Williams Medical Center

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms; Stomach Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Richard P Junghans, PhD, MD

  Roger Williams Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 7, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2016
• Study Completion: August 1, 2017
• Last Updated: June 14, 2016

Record last verified: 2016-06

Locations

US (1)