Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART-meso

Phase 1

• Conditions: Triple Negative Breast Cancer; Pancreatic Cancer; Malignant Mesothelioma; Endometrial Cancer; Other Mesothelin Positive Tumors; Ovarian Tumor
• Interventions: Biological: anti-meso-CAR vector transduced T cells

• Registration Number: NCT02580747
• Lead Sponsor: Chinese PLA General Hospital

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.

Detailed Description

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).

Study Timeline

• Status Verified: 2015-10
• Study Start: 2015-10
• Study First Submitted: 2015-10-19
• Study First Submitted QC: 2015-10-19
• Last Update Submitted: 2015-10-19
• Study First Posted: 2015-10-20
• Last Update Posted: 2015-10-20
• Primary Completion: 2017-11
• Study Completion: 2018-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Chemotherapy refractory or relapsed mesothelin positive malignant mesothelioma,ovarian tumors,pancreatic cancer,triple negative breast cancer,endometrial cancer and other mesothelin positive tumor

2. Patients must be 18 years of age or older.

3. Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.

4. 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.

5. Seronegative for HIV antibody.

6. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.

7. 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.

8. Patients must be willing to sign an informed consent.

Exclusion Criteria

1. Patients with life expectancy less than 12 months will be excluded.
2. 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.
3. 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.
4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
5. Pregnant and/or lactating women will be excluded.
6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
7. Patients with any type of primary immunodeficiencies will be excluded from the study.
8. Patients requiring corticosteroids (other than inhaled) will be excluded.
9. Patients with history of T cell tumors will be excluded.
10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-meso CAR T cells	anti-meso-CAR vector transduced 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.

Primary Outcome Measures

Name	Time	Method
Occurrence of Study related adverse events	Until week 24	defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical

Secondary Outcome Measures

Name	Time	Method
Anti-tumor responses to CART-meso cell infusions	up to 24 weeks

Trial Locations

Locations (1)

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China