Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma

Phase 1

Recruiting

• Conditions: Immunotherapy
• Interventions: Biological: CAR-T cell immunotherapy

• Registration Number: NCT04969354
• Lead Sponsor: The Affiliated Hospital of Xuzhou Medical University

Brief Summary

This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.

Detailed Description

We designed a clinical study and divided the trial into two phases.

Phase 1 (climbing test) : 12 patients were randomly divided into 4 groups (n=3). 12 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m\^2/d 6-2 days before CAR-T cell infusion. 5 mg anti-human CAIX monoclonal antibody (G250) was injected into the hepatic artery of each patient by an interventional catheter on the day before CAR-T cells infusion. On Day 0, CAR T cells were injected into patients in group 1, 2, 3 or 4 at the dose of 1x10\^7/ person, 1\*10\^8/ person, 1\*10\^9/ person or 1\*10\^10/ person, respectively. The infusion time is about 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.

Phase 2: After determining the appropriate therapeutic dose for patients with renal cell carcinoma, 8 patients received the same pre-treatment of chemotherapy and G250 antibody. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.

Peripheral blood was collected every 4 weeks to evaluate proliferation and survival of CAR-T cells. After 6 months of close follow-up, subjects will undergo a medical history evaluation, physical examination, and blood tests quarterly for 2 years. After this assessment, subjects will be enrolled in an annual telephone follow-up and questionnaire study for up to five years to evaluate treatment for long-term health problems, such as recurrence of malignant tumors.

Study Timeline

• Status Verified: 2021-07
• Study First Submitted: 2021-07-04
• Study First Submitted QC: 2021-07-17
• Last Update Submitted: 2021-07-17
• Study First Posted: 2021-07-20
• Last Update Posted: 2021-07-20
• Study Start: 2021-10-01
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Male or female patients aged from 18 to 70 years old;
2. The patient's ECOG score is ≤ 2;
3. Patients with advanced or metastatic renal cell carcinoma:

(1) have received first-line and second-line targeted therapy in the past; (2) Previous immunization with PD-1/L1 and ≤2 regimens; (3) Unable to tolerate targeted therapy or immunotherapy. 4.There are measurable or evaluable lesions; 5.The main tissues and organs of patients function well:

1. liver function: ALT/AST< 3 times the upper limit of normal value (ULN);
2. Renal function: creatinine < 220 μmol/L;
3. Lung function: indoor oxygen saturation ≥ 95%;
4. Cardiac function: Left ventricular ejection fraction (LVEF)≥40% 6.Patients or their legal guardians voluntarily participate and sign informed consent.

Exclusion Criteria

1. Infectious diseases (such as HIV, active hepatitis B or C infection, active tuberculosis, etc.);
2. Feasibility assessment and screening showed that the transfection of targeted lymphocytes was less than 10% or the amplification was insufficient (< 5 times) under the co-stimulation of CD3/CD28.
3. The vital signs are abnormal, and those who cannot cooperate with the examination;
4. Those who have mental or psychological diseases can not cooperate with treatment and efficacy evaluation;
5. Highly allergic constitution or severe allergic history, especially those who are allergic to IL-2;
6. Subjects with systemic infection or severe local infection who need anti-infection treatment;
7. Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs;
8. Patients with other tumors;
9. Doctors believe that there are other reasons that can not be included in the treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T cell immunotherapy	CAR-T cell immunotherapy	The registered patients will received CAR-T cell immunotherapy for the new specific chimeric antigen receptor of CAIX antigen by infusion.

Primary Outcome Measures

Name	Time	Method
Effectiveness evaluation	3 months after CAR-T cells infusion	In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.
Safety evaluation:Incidence and severity of adverse events	First 1 month after CAR-T cells infusion	To evaluate the incidence and severity of possible adverse events within one month after targeted CAIX CAR-T infusion, including cytokine release syndrome and on-target toxicity.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	24 months after CAR-T cells infusion	Overall survival (OS) time
Progression-free survival (PFS)	24 months after CAR-T cells infusion	Progression-free survival (PFS) time

Trial Locations

Locations (1)

Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, Jiangsu, China