Genetically Modified T Cells Treating Malignant Tumors

Clinical Study to Evaluate the Safety and Efficacy of Genetically Modified T Cells in the Treatment of Malignant Tumors

To observe the safety, tolerability and initial effectiveness of gene modified T cell therapy in patients with malignant tumors in First Affiliated Hospital of Zhengzhou University, China.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: CAR-T cell reinfusion

Detailed Description

The study population included subjects with malignant tumors confirmed by histopathology or cytology, including: non-small cell lung cancer, esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, kidney cancer, cervical squamous cell carcinoma, ovarian cancer, breast cancer, melanoma, brain glioma, lymphoma, etc.

The study is aimed to observe the safety, tolerability and initial effectiveness of gene modified T cell therapy in patients with malignant tumors.To observe Progression-Free Survival (PFS) and Overall survival (OS) after the application of gene modified T cell therapy in patients with malignant tumors, and to evaluate the Disease Control Rate (Disease Control Rate). DCR, Clinical Benefit Rate (CBR), Quality of Life (QOL).And explore the diversity of T cell receptors and proportion of lymphocyte subsets in subjects treated with gene-modified T cell therapy for malignant tumors changes in distribution and count, immune cell function, and serum cytokine levels.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yi Zhang, MD; Phone Number: +86 15138928971; Email: yizhang@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Zhengzhou university first affiliated hospital
      • Contact: Yi Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects with malignant tumors confirmed by histopathology or cytology, including: non-small cell lung cancer, esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, kidney cancer, cervical squamous cell carcinoma, ovarian cancer, breast cancer, melanoma, and brain glia tumor, lymphoma, etc.;
2. Age: 18 ~ 75 years old; Gender: no limitation;
3. Have sufficient hematopoietic capacity: ANC >1500 cells /mm3, Blood plate count >50,000 cells /mm3, HGB >9.0g/dL, ALC >9 cells /mm3;
4. Adequate liver and kidney function: AST and ALT ≤2.5 ULN in patients without liver metastasis and ≤5 times in patients with liver metastasis. ULN; Bilirubin ≤1.5 ULN (excluding hyperbilirubinemia or hyperbilirubin of non-hepatic origin); Creatinine ≤2.0 ULN. Creatinine clearance and creatinine clearance hormone ≥40 mL/min;
5. PT/INR <1.5 ULN, and PTT/αPTT <1.5 ULN;
6. For desirable tumor tissues or tissue white tablets, positive expression of at least one of Mesothelin, NKG2D, HER2, CD276, CD19, BCMA and other antigens can be selected for clinical trials;
7. ECOG physical status score 0 ~ 2 points;
8. Expected survival >6 months;
9. Subject accepts voluntarily

Exclusion Criteria:

1. Received anti-PD1, anti-PD-L1 or anti-PD-L2 antibody therapy or other immunotherapy methods one month before treatment with immune cells in this study;
2. History of organ transplantation;
3. Pregnancy or lactation;
4. Positive for high baseline HBV DNA levels (≥2000 IU/ml), HIV antibodies (anti-HIV), hepatitis C virus antibodies (anti-HCV), or treponema pallidum antibodies;
5. There is active infection;
6. There are active brain metastases (except asymptomatic or stable brain metastases after treatment);
7. Combined with a second tumor; With the exception of patients with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ, or papillary thyroid cancer who achieved complete response to the second tumor for more than 5 years and did not require treatment during the study period;
8. Severe autoimmune diseases such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune vasculitis, or Wegener's granulomatosis require long-term (more than 2 months) systemic immunosuppressive therapy;
9. People with allergies;
10. NYHA heart failure grade ≥2 or hypertension can not be controlled after standard treatment, have a history of myocarditis or have a heart attack within one year;
11. Thrombotic diseases with active bleeding that require treatment;
12. Patients who are determined by the researcher to have a serious uncontrollable disease or other conditions that may affect the treatment in this study and are considered unsuitable.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: subject

Biological: CAR-T cell reinfusion; Subjects were identified according to their benefit from the first treatment and target expression Whether to accept multiple returns; CAR-T cell reinfusion dose was 1~10×106 cells/kg, and the reinfusion dose could be adjusted according to the tolerance of the subjects Usually intravenous infusion, but also according to the need for local interventional treatment or injection treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-Free-Survival (PFS) is defined as admission to the group according to imaging specialists based on RECIST 1.1 review when disease progression or death from any cause was first recorded, whichever came first.	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS) is the time from enrollment to death from any cause	up to 36 months
ORR	Objective response rate（ORR） refers to the proportion of subjects in the analysis population who achieved complete response (CR) or partial response (PR).	up to 36 months
DOR	Duration of response (DOR). For subjects with confirmed CR or PR, duration of remission is the time from first recording to evidence of CR or PR until disease 2 progression (according to RECIST 1.1) or death from any cause, whichever occurs first.	up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life improvement	EORTC QLQ C-30 survey	Baseline,The first day of each course (before dosing),up to 4weeks .

Collaborators and Investigators

• Sponsor: Yi Zhang
• Investigators: Study Chair: Yi Zhang, MD, The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: CAR
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: YiZhang

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No