Anti-CD70-CAR-T Cell Injection for the Treatment of Locally Advanced or Relapsed/Metastatic CD70+ Inoperable Renal Cells

NCT06586658 | Recruiting Early Phase 1

• 1 other identifier: CD70-CN-A5
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the role of anti-CD70-CAR T cells in locally advanced or recurrent/metastatic renal cell carcinoma that is inoperable.

Conditions

Renal Cell Carcinoma

Keywords

CART; CD70; Renal carcinoma

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT) within 28 days after infusion

  Within 28 days after infusion

• Incidence and severity of adverse events after infusion (including abnormal test values, physical examination, vital sign parameters)

  1 year

• Maximum tolerated dose (MTD) or recommended dose in subsequent clinical trials

  Up to 28 days from CAR-T infusion

Secondary Outcomes (3)

• Progression-free survival (PFS)

  From date of CAR-T infusion until date of first documented progression or date of death from any cause, whichever came first, assessed up to 15 years

• Overall survival (OS)

  From date of CAR-T infusion until date of death from any cause, assessed up to 15 years

• Duration of efficacy (DOR)

  Through study completion, an average of 1 year

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

Biological: anti-CD70-CAR-T cells

Interventions

anti-CD70-CAR-T cells BIOLOGICAL

The subjects received infusions of anti-CD70 CART cells following completion of lymphodepleting preconditioning chemotherapy. Dosage: 3×10\^6 cells/Kg; 1×10\^7 cells/Kg; 2×10\^7 cells/Kg.

Assigned Interventions

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and sign informed consent, and voluntarily participate in clinical research;
• Age ≥18, and \<70 years old, gender is not limited;
• Histopathologically or cytologically confirmed advanced malignant renal cell carcinoma of CD70+ with at least VEGFR-targeted therapy and an immune checkpoint therapy (either combination therapy or sequential therapy);
• At least one measurable lesion with a maximum diameter of less than 6 cm according to RECIST 1.1;
• Expected survival ≥12 weeks;
• ECOG score ≤2 points;
• Have sufficient hematologic function and have not received blood transfusion or cell growth factor therapy within 7 days prior to the hematologic evaluation during the screening period (2 weeks interval is required for those receiving long-acting agents such as PEG-rhG-CSF, allowing the use of recombinant erythropoietin) :
• Neutrophil absolute value ≥1.5×109/L
• Hemoglobin ≥80g/L
• Platelets ≥75×109/L
• Lymphocytes (ALC) ≥0.3×109/L
• Adequate liver function: serum total bilirubin ≤1.5× upper limit of normal (ULN) (for Gilbert syndrome patients, total bilirubin ≤3×ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5×ULN; If there is liver metastasis, allow AST, ALT≤5×ULN);
• Adequate renal function: creatinine ≤1.5×ULN or endogenous creatinine clearance ≥50 mL/min (using Cockcroft Gault formula);
• Left ventricular ejection fraction (LVEF) of echocardiography was ≥50%.
• There was no evidence of dyspnea at rest and pulse oximetry was \>93% without oxygen.

You may not qualify if:

• Patients are not eligible to participate in this trial if they meet any of the following conditions:
• Previous use of any CAR T cell products or other genetically modified T cell therapy;
• Patients who have a history of allogeneic stem cells or solid organ transplantation or are waiting for organ transplantation;
• Patients with acute or uncontrolled active infection who currently require intravenous anti-infective therapy, and patients taking antibiotics to prevent infection should be allowed to participate in the study at the discretion of the investigator;
• Active hepatitis B (hepatitis B surface antigen positive and hepatitis B DNA\>103 copies /mL or \>200IU/mL), active hepatitis C (hepatitis C antibody positive and RNA positive); Active syphilis infection (RPR or TRUst-positive), human immunodeficiency virus (HIV) infection (HIV positive);
• Patients with low sodium and/or hypokalemia with blood sodium \<125mmol/L and/or blood potassium \<3.5mmol/L (unless sodium and/or potassium supplementation is required prior to study participation to restore blood sodium and/or potassium above this level);
• Imaging results showed that the proportion of liver replaced by tumor was ≥50%;
• Previously received anti-CD70 therapy;
• Receiving continuous systemic steroid medication (prednisone \> 10mg/ day or equivalent dose of other hormones) within 14 days of preapheresis or 3 days before cell therapy, except for recent or current topical steroid use;
• Toxicity from previous antitumor therapy has not recovered (\>CTCAE version 5.0 Grade 1), except for alopecia, pigmentation, and other tolerable events as determined by the investigator or laboratory abnormalities permitted under the protocol;
• The eluting period of preaphermative antitumor therapy met the following requirements:
• ≦2 weeks or 5 half-lives of chemotherapy, small molecule targeted therapy, radiotherapy, endocrine therapy, immunomodulatory therapy, and Chinese medicine with anti-tumor indications
• ≦4 weeks of macromolecular targeted therapy and immunotherapy
• ≦4 weeks of anti-tumor vaccine
• ≦4 weeks of investigational medication/therapy

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead
• Shanghai First Song Biotechnology Co., LTD: collaborator

Study Sites (1)

Changzheng hospital

Shanghai, Shanghai Municipality, 201109, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Shancheng Ren, MD,PhD

  Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shancheng Ren, MD,PhD

CONTACT

139 1779 3885; renshancheng@gmail.com

Zhixiang Xin, MD

CONTACT

13636391268; xiaoxin973@hotmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief of Urology

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: September 19, 2024
• Study Start: September 6, 2024
• Primary Completion (Estimated): July 16, 2027
• Study Completion (Estimated): July 16, 2027
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)