Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART-meso
Study Details
Study Description
Brief Summary
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with Relapsed and/or Chemotherapy Refractory Advanced Malignancies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-meso vector (referred to as CART-meso cells).
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Determine duration of in vivo survival of CART-meso cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-meso TCR (T-cell receptor) zeta:CD137 over time.
SECONDARY OBJECTIVES:
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For patients with detectable disease, measure anti-tumor response due to CART-meso cell infusions.
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Estimate relative trafficking of CART-meso cells to tumor in bone marrow and lymph nodes.
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For patients with stored or accessible tumor cells determine tumor cell killing by CART-meso cells in vitro.
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Determine if cellular or humoral host immunity develops against the murine anti-meso, and assess correlation with loss of detectable CART-meso (loss of engraftment).
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Determine the relative subsets of CART-meso T cells (Tcm, Tem, and Treg).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: anti-meso CAR T cells Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Patients receive anti-meso-CAR retroviral vector-transduced autologous-derived T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity. |
Biological: anti-meso-CAR vector transduced T cells
genetically engineered lymphocyte therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Occurrence of Study related adverse events [Until week 24]
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical
Secondary Outcome Measures
- Anti-tumor responses to CART-meso cell infusions [up to 24 weeks]
Other Outcome Measures
- In vivo existence of CART-meso [1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Chemotherapy refractory or relapsed mesothelin positive malignant mesothelioma,ovarian tumors,pancreatic cancer,triple negative breast cancer,endometrial cancer and other mesothelin positive tumor
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Patients must be 18 years of age or older.
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Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
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Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:
Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).
Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m.
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Seronegative for HIV antibody.
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Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
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Patients must be willing to practice birth control during and for four months following treatment. NOTE: women of child-bearing age must have evidence of negative pregnancy test.
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Patients must be willing to sign an informed consent.
Exclusion Criteria:
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Patients with life expectancy less than 12 months will be excluded.
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Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.
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Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
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Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
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Pregnant and/or lactating women will be excluded.
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Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
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Patients with any type of primary immunodeficiencies will be excluded from the study.
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Patients requiring corticosteroids (other than inhaled) will be excluded.
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Patients with history of T cell tumors will be excluded.
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Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital | Beijing | Beijing | China | 100853 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- s2015-080-06