search
Back to results

The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
anti- MESO CAR-T cells
Fludarabine
Cyclophosphamide
Sponsored by
Shanghai 6th People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring MESO, CAR-T, Ovarian cancer, Refractory-Relapsed

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histopathologically confirmed ovarian cancer;
  2. 18-75 Years Old, female;
  3. Expected survival > 12 weeks;
  4. Eastern Cooperative Oncology Group (ECOG) score 0-2;
  5. Patients who have previously been treated with second- line or above standard treatment are failed (progress in treatment or recurrence within 6 months after discontinuation of treatment);
  6. According to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST) , there should be at least one measurable tumor foci；
  7. Positive expression of Mesothelin in tumor tissue；
  8. Creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60ml / min;
  9. alanine aminotransferase and aspartate aminotransferase ≤ 2.5×ULN , such as with liver metastasis, ≤ 5×ULN;
  10. Total bilirubin ≤ 2×ULN;
  11. Hemoglobin≥90g/L(No blood transfusion within 14 days);
  12. Absolute value of neutrophils ≥1.5×10^9/L;
  13. Absolute counting of lymphocytes >0.7×10^9/L;
  14. Counting of Platelet≥80×10^9/L；
  15. The venous access required for collection can be established without contraindications for leukocyte collection;
  16. Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

  1. Accompanied by other uncontrolled malignant tumors;
  2. Active hepatitis B, hepatitis C, syphilis, HIV infection;
  3. Insufficient function of important organs (heart, lung);
  4. Any other uncontrolled active disease that impedes participation in the trial;
  5. Any affairs could affect the safety of the subjects or purpose this trial;
  6. Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment;
  7. There are active or uncontrollable infections (except simple urinary tract infections or upper respiratory tract infections) that require systemic therapy within 14 days or 14 days prior to enrollment；
  8. The investigator believes that it is not appropriate to participate in the trial;
  9. Received CAR-T treatment or other gene therapies before enrollment; Subjects suffering disease affect the understanding of informed consent or unable to comply with study; Unwilling or unable to comply with study requirements.

Sites / Locations

  • Shanghai 6th People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti- MESO CAR-T cells

Arm Description

The subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d d-4~-2. Then anti- MESO CAR-T cells will be injected by a dose of 5×106/kg once at d1(rang from d1-3).

Outcomes

Primary Outcome Measures

Adverse events (AEs) and Serious adverse event (SAEs)
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03

Secondary Outcome Measures

Cmax
the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration
Tmax
the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration
AUC(0-30d)
the area under the curve of 30 days of anti-human MESO T cells in the peripheral blood after administration
Duration of Mesothelin-positive T cells in circulation
Duration of Mesothelin-positive T cells in circulation
ORR
Overall response rate after administration
PFS
Progress Free Survival after administration
EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration
This QLQ-C15-PAL score consists of 15 questions; two multi-item functional scales (physical and emotional functioning), two multi-item symptom scales (fatigue and pain) together with five single-item symptom scales (nausea/vomiting, dyspnea, insomnia, appetite loss, constipation) and one final question referring to overall QOL. The physical functioning scale is based on three questions regarding walking, activities of daily living and time spent in bed or in a chair. The emotional functioning scale is based on two questions that ask about feeling tense or depressed. Patients rated each question on a Likert scale from 1 (not at all) to 4 (very much), with the exception of overall QOL, which was rated from 1 (very poor) to 7 (excellent)

Full Information

First Posted
January 18, 2019
Last Updated
August 9, 2021
Sponsor
Shanghai 6th People's Hospital
Collaborators
Hrain Biotechnology Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT03814447
Brief Title
The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian Cancer
Official Title
The Clinical Research of Fourth Generation CART-cell Therapy in Refractory-Relapsed Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 16, 2019 (Actual)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai 6th People's Hospital
Collaborators
Hrain Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to study the safety and feasibility of anti- Mesothelin Chimeric Antigen Receptor T-Cell (MESO CAR-T cells) therapy for Refractory-Relapsed Ovarian Cancer
Detailed Description
Primary Objectives: 1. To determine the safety and feasibility of anti- MESO CAR-T cells therapy for Refractory-Relapsed Ovarian Cancer Secondary Objectives: To access the efficacy of anti- MESO CAR-T cells in patients with ovarian cancer. To determine in vivo dynamics and persistency of anti- MESO CAR-T cells To assess the quality of life in patients with ovarian cancer after treatment with anti- MESO CAR-T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
MESO, CAR-T, Ovarian cancer, Refractory-Relapsed

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
anti- MESO CAR-T cells
Arm Type
Experimental
Arm Description
The subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d d-4~-2. Then anti- MESO CAR-T cells will be injected by a dose of 5×106/kg once at d1(rang from d1-3).
Intervention Type
Drug
Intervention Name(s)
anti- MESO CAR-T cells
Intervention Description
Autologous genetically modified anti- MESO CAR transduced T cells
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
FA
Intervention Description
Dose: 30mg/m2/d
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
CTX
Intervention Description
Dose: 300mg/m2/d
Primary Outcome Measure Information:
Title
Adverse events (AEs) and Serious adverse event (SAEs)
Description
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03
Time Frame
1 year post infusion
Secondary Outcome Measure Information:
Title
Cmax
Description
the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration
Time Frame
30 days post infusion
Title
Tmax
Description
the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration
Time Frame
30 days post infusion
Title
AUC(0-30d)
Description
the area under the curve of 30 days of anti-human MESO T cells in the peripheral blood after administration
Time Frame
30 days post infusion
Title
Duration of Mesothelin-positive T cells in circulation
Description
Duration of Mesothelin-positive T cells in circulation
Time Frame
90 days post infusion
Title
ORR
Description
Overall response rate after administration
Time Frame
3 months post infusion
Title
PFS
Description
Progress Free Survival after administration
Time Frame
1 year post infusion
Title
EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration
Description
This QLQ-C15-PAL score consists of 15 questions; two multi-item functional scales (physical and emotional functioning), two multi-item symptom scales (fatigue and pain) together with five single-item symptom scales (nausea/vomiting, dyspnea, insomnia, appetite loss, constipation) and one final question referring to overall QOL. The physical functioning scale is based on three questions regarding walking, activities of daily living and time spent in bed or in a chair. The emotional functioning scale is based on two questions that ask about feeling tense or depressed. Patients rated each question on a Likert scale from 1 (not at all) to 4 (very much), with the exception of overall QOL, which was rated from 1 (very poor) to 7 (excellent)
Time Frame
1 year post infusion

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histopathologically confirmed ovarian cancer; 18-75 Years Old, female; Expected survival > 12 weeks; Eastern Cooperative Oncology Group (ECOG) score 0-2; Patients who have previously been treated with second- line or above standard treatment are failed (progress in treatment or recurrence within 6 months after discontinuation of treatment); According to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST) , there should be at least one measurable tumor foci； Positive expression of Mesothelin in tumor tissue； Creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60ml / min; alanine aminotransferase and aspartate aminotransferase ≤ 2.5×ULN , such as with liver metastasis, ≤ 5×ULN; Total bilirubin ≤ 2×ULN; Hemoglobin≥90g/L(No blood transfusion within 14 days); Absolute value of neutrophils ≥1.5×10^9/L; Absolute counting of lymphocytes >0.7×10^9/L; Counting of Platelet≥80×10^9/L； The venous access required for collection can be established without contraindications for leukocyte collection; Able to understand and sign the Informed Consent Document. Exclusion Criteria: Accompanied by other uncontrolled malignant tumors; Active hepatitis B, hepatitis C, syphilis, HIV infection; Insufficient function of important organs (heart, lung); Any other uncontrolled active disease that impedes participation in the trial; Any affairs could affect the safety of the subjects or purpose this trial; Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment; There are active or uncontrollable infections (except simple urinary tract infections or upper respiratory tract infections) that require systemic therapy within 14 days or 14 days prior to enrollment； The investigator believes that it is not appropriate to participate in the trial; Received CAR-T treatment or other gene therapies before enrollment; Subjects suffering disease affect the understanding of informed consent or unable to comply with study; Unwilling or unable to comply with study requirements.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Zhao, doctor
Phone
021-64369181
Email
ivy25502@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yincheng Teng, doctor
Phone
021-64369181
Email
teng_yc@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hui Zhao, doctor
Organizational Affiliation
Shanghai 6th People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai 6th People's Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui Zhao
Phone
021-64369181
Email
ivy25502@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian Cancer

We'll reach out to this number within 24 hrs