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

Ovarian Cancer Clinical Trial

Official title:

The Clinical Research of Fourth Generation CART-cell Therapy in Refractory-Relapsed Ovarian Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03814447
• Other study ID #: MESO-CART
• Status: Recruiting
• Phase: Early Phase 1
• Start date: August 16, 2019
• Est. completion date: January 2023

Study information

• Verified date: August 2021
• Source: Shanghai 6th People's Hospital
• Contact: Hui Zhao, doctor
• Phone: 021-64369181
• Email: ivy25502[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Primary Objectives:

1. To determine the safety and feasibility of anti- MESO CAR-T cells therapy for Refractory-Relapsed Ovarian Cancer

Secondary Objectives:

1. To access the efficacy of anti- MESO CAR-T cells in patients with ovarian cancer.

2. To determine in vivo dynamics and persistency of anti- MESO CAR-T cells

3. To assess the quality of life in patients with ovarian cancer after treatment with anti- MESO CAR-T cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 2023
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• anti- MESO CAR-T cells
Autologous genetically modified anti- MESO CAR transduced T cells
• Fludarabine
Dose: 30mg/m2/d
• Cyclophosphamide
Dose: 300mg/m2/d

Locations

Country	Name	City	State
China	Shanghai 6th People's Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai 6th People's Hospital	Hrain Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events (AEs) and Serious adverse event (SAEs)	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03	1 year post infusion
Secondary	Cmax	the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration	30 days post infusion
Secondary	Tmax	the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration	30 days post infusion
Secondary	AUC(0-30d)	the area under the curve of 30 days of anti-human MESO T cells in the peripheral blood after administration	30 days post infusion
Secondary	Duration of Mesothelin-positive T cells in circulation	Duration of Mesothelin-positive T cells in circulation	90 days post infusion
Secondary	ORR	Overall response rate after administration	3 months post infusion
Secondary	PFS	Progress Free Survival after administration	1 year post infusion
Secondary	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)	1 year post infusion