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

July 17, 2021 updated by: The Affiliated Hospital of Xuzhou Medical University
This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Xuzhou, Jiangsu, China, 221000
        • Recruiting
        • Affiliated Hospital of Xuzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: CAR-T cell immunotherapy
This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at CAIX antigen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety evaluation:Incidence and severity of adverse events
Time Frame: 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.
First 1 month after CAR-T cells infusion
Effectiveness evaluation
Time Frame: 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.
3 months after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 24 months after CAR-T cells infusion
Progression-free survival (PFS) time
24 months after CAR-T cells infusion
Overall survival (OS)
Time Frame: 24 months after CAR-T cells infusion
Overall survival (OS) time
24 months after CAR-T cells infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Affiliated Hospital of Xuzhou Medical University

Collaborators

Xuzhou Medical University

Investigators

  • Study Director: Junnian Zheng, M.D/Ph.D, The Affiliated Hospital of Xuzhou Medical University
  • Principal Investigator: Hailong Li, M.D/Ph.D, The Affiliated Hospital of Xuzhou Medical University
  • Principal Investigator: Qing Zhang, Ph.D, Xuzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2021

Primary Completion (Anticipated)

September 30, 2025

Study Completion (Anticipated)

September 30, 2026

Study Registration Dates

First Submitted

July 4, 2021

First Submitted That Met QC Criteria

July 17, 2021

First Posted (Actual)

July 20, 2021

Study Record Updates

Last Update Posted (Actual)

July 20, 2021

Last Update Submitted That Met QC Criteria

July 17, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XYFY2021-KL092-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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