search
Back to results

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

Primary Purpose

Malignant Mesothelioma, Pancreatic Cancer, Ovarian Tumor

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-meso-CAR vector transduced T cells
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Mesothelioma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Biotherapeutic Department and Pediatrics Department of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-meso CAR T cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Occurrence of Study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical

Secondary Outcome Measures

Anti-tumor responses to CART-meso cell infusions

Full Information

First Posted
October 19, 2015
Last Updated
October 19, 2015
Sponsor
Chinese PLA General Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02580747
Brief Title
Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART-meso
Official Title
Clinical Study of Chimeric Mesothelin Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Unknown status
Study Start Date
October 2015 (undefined)
Primary Completion Date
November 2017 (Anticipated)
Study Completion Date
November 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Mesothelioma, Pancreatic Cancer, Ovarian Tumor, Triple Negative Breast Cancer, Endometrial Cancer, Other Mesothelin Positive Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-meso CAR T cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
anti-meso-CAR vector transduced T cells
Other Intervention Name(s)
genetically engineered lymphocyte therapy
Intervention Description
genetically engineered lymphocyte therapy
Primary Outcome Measure Information:
Title
Occurrence of Study related adverse events
Description
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical
Time Frame
Until week 24
Secondary Outcome Measure Information:
Title
Anti-tumor responses to CART-meso cell infusions
Time Frame
up to 24 weeks
Other Pre-specified Outcome Measures:
Title
In vivo existence of CART-meso
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Patients with life expectancy less than 12 months will be excluded. 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. 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. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded. Pregnant and/or lactating women will be excluded. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors. Patients with any type of primary immunodeficiencies will be excluded from the study. Patients requiring corticosteroids (other than inhaled) will be excluded. Patients with history of T cell tumors will be excluded. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weidong Han, Dr.
Phone
86-10-13651392893
Email
hanwdrsw@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yao Wang, Dr.
Phone
86-10-13311390785
Email
wangyao301@163.com
Facility Information:
Facility Name
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weidong Han, Dr.
Phone
86-10-66937463
Email
hanwdrsw@sina.com
First Name & Middle Initial & Last Name & Degree
Yao Wang, Dr.
Phone
86-10-66937376
Email
wangyao301@163.com
First Name & Middle Initial & Last Name & Degree
Yao Wang, Dr.

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs