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

Sponsor

Shanghai 6th People's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03814447

Collaborator

Hrain Biotechnology Co., Ltd. (Industry)

Enrollment

Location

Arm

40.5

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: anti- MESO CAR-T cells Drug: Fludarabine Drug: Cyclophosphamide	Early Phase 1

Detailed Description

Primary Objectives:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 16, 2019

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anti- MESO CAR-T cells 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).	Drug: anti- MESO CAR-T cells Autologous genetically modified anti- MESO CAR transduced T cells Drug: Fludarabine Dose: 30mg/m2/d Other Names: FA Drug: Cyclophosphamide Dose: 300mg/m2/d Other Names: CTX

Arm

Intervention/Treatment

Experimental: anti- MESO CAR-T cells

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).

Drug: anti- MESO CAR-T cells

Autologous genetically modified anti- MESO CAR transduced T cells

Drug: Fludarabine

Dose: 30mg/m2/d

Other Names:

Drug: Cyclophosphamide

Dose: 300mg/m2/d

Other Names:

CTX

Outcome Measures

Primary Outcome Measures

Adverse events (AEs) and Serious adverse event (SAEs) [1 year post infusion]
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.03

Secondary Outcome Measures

Cmax [30 days post infusion]
the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after administration
Tmax [30 days post infusion]
the time to reach the highest concentration (Tmax) of anti-human MESO T cells in the peripheral blood after administration
AUC(0-30d) [30 days post infusion]
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 [90 days post infusion]
Duration of Mesothelin-positive T cells in circulation
ORR [3 months post infusion]
Overall response rate after administration
PFS [1 year post infusion]
Progress Free Survival after administration
EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration [1 year post infusion]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.