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

Pancreatic Cancer Clinical Trial

Official title:

Clinical Study of Chimeric Mesothelin Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02580747
• Other study ID #: s2015-080-06
• Status: Recruiting
• Phase: Phase 1
• First received: October 19, 2015
• Last updated: October 19, 2015
• Start date: October 2015
• Est. completion date: November 2018

Study information

• Verified date: October 2015
• Source: Chinese PLA General Hospital
• Contact: Weidong Han, Dr.
• Phone: 86-10-13651392893
• Email: hanwdrsw[@]sina.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma
• Other Mesothelin Positive Tumors
• Ovarian Neoplasms
• Ovarian Tumor
• Pancreatic Cancer
• Pancreatic Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• anti-meso-CAR vector transduced T cells
genetically engineered lymphocyte therapy

Locations

Country	Name	City	State
China	Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	In vivo existence of CART-meso		1 year	Yes
Primary	Occurrence of Study related adverse events	defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical	Until week 24	Yes
Secondary	Anti-tumor responses to CART-meso cell infusions		up to 24 weeks	No