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

Shanghai Jiao Tong University

Status and phase: Unknown; Early Phase 1

Conditions: Ovarian Cancer

Treatments: Drug: Fludarabine; Drug: anti- MESO CAR-T cells; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03814447

MESO-CART

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

anti- MESO CAR-T cells

Experimental group

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).

Treatment:

Drug: Cyclophosphamide

Drug: anti- MESO CAR-T cells

Drug: Fludarabine