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

Phase 1

Recruiting

• Conditions: 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

Primary Outcome Measures

Name	Time	Method
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.
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.

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