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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.
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-meso vector (referred to as CART-meso cells).
II. 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:
I. For patients with detectable disease, measure anti-tumor response due to CART-meso cell infusions.
II. Estimate relative trafficking of CART-meso cells to tumor in bone marrow and lymph nodes.
III. For patients with stored or accessible tumor cells determine tumor cell killing by CART-meso cells in vitro.
IV. 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).
V. Determine the relative subsets of CART-meso T cells (Tcm, Tem, and Treg).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| anti-meso CAR T cells | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-meso-CAR vector transduced T cells | Biological | genetically engineered lymphocyte therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Study related adverse events | defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical | Until week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-tumor responses to CART-meso cell infusions | up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| In vivo existence of CART-meso | 1 year |
Inclusion Criteria:
Chemotherapy refractory or relapsed mesothelin positive malignant mesothelioma,ovarian tumors,pancreatic cancer,triple negative breast cancer,endometrial cancer and other mesothelin positive tumor
Patients must be 18 years of age or older.
Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
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.
Seronegative for HIV antibody.
Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
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.
Patients must be willing to sign an informed consent.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, Dr. | Contact | 86-10-13651392893 | hanwdrsw@sina.com | |
| Yao Wang, Dr. | Contact | 86-10-13311390785 | wangyao301@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
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| ID | Term |
|---|---|
| D000086002 | Mesothelioma, Malignant |
| D010190 | Pancreatic Neoplasms |
| D010051 | Ovarian Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D008654 | Mesothelioma |
| D000236 | Adenoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018301 | Neoplasms, Mesothelial |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D010997 | Pleural Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004067 | Digestive System Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D001943 | Breast Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014594 | Uterine Neoplasms |
| D014591 | Uterine Diseases |
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