NKG2D-based CAR T-cells Immunotherapy for Patient With r/r NKG2DL+ Solid Tumors

A Phase I Clinical Trial of NKG2D-based CAR T-cells Injection for Subjects With Relapsed/Refractory NKG2DL+ Solid Tumors

The primary objective of this study is to evaluate the safety and clinical activity of NKG2D-based CAR-T cells infusion in the treatment of relapsed/refractory NKG2DL+ solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Hepatocellular Carcinoma; Medulloblastoma; Colon Cancer
• Intervention / Treatment: Biological: NKG2D-based CAR T-cells

Detailed Description

The preclinical study clarified that NKG2D-based CAR-T cells showed strong cytotoxicity against NKG2DL+ cell lines in vitro as well as a therapeutic effect against NKG2DL+ cell xenografts in vivo. In addition, the data also demonstrated the safety of NKG2D-based CAR-T therapy. NKG2D-based CART represent a potentially effective and safety therapeutic approach for patient with relapsed/refractory NKG2DL+ solid tumors. In this trial, the investigators researched the safety of administering NKG2D-based CAR-T which generated with CD8 hinge region and transmembrane region, 4-1BB costimulatory region and CD3 zeta region. The investigators also assessed that disease response was determined within the context of a phase I trial.

• Study Type: Interventional
• Enrollment (Anticipated): 3
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hui Xu; Phone Number: 13337719185; Email: huixu1989@163.com
• Study Contact Backup: Name: Jiaying Deng, doctor; Phone Number: 18017312829; Email: dengjiaying3@sina.com

Study Locations

• China
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Recruiting
      • Xunyang Changchun Shihua Hospital
      • Contact: Changchun Cai, doctor; Phone Number: 13870257887; Email: m13870257887@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women≥18 years old,
2. Patient with NKG2DL+ cell tumors confirmed by pathology and histology,
3. Fail or unwilling to receive first-line treatment,
4. Disease must be measurable according to the corresponding guidelines,

5. Main organs function normally and meet following requirements:

   Routine blood index#No Blood transfusion within 14 days# 1)HB≥90g/ L; 2)ANC≥1.5×109/L; 3)PLT≥75×109/L# Serum biochemicals index 1) BIL <1.5 upper normal limit (ULN); 2) ALT and AST<2.5×ULN; In the case of liver metastasis, ALT and AST<5×ULN; 3) Serum Cr≤1×ULN, endogenous creatinine clearance≥50ml/min (Cockcroft-Gault formula); 4) ECOG physical condition score: 0-2

6. Expected survival time ≥3 months,
7. Patient with adequate bone marrow reserve, hepatic and renal functions,
8. No other uncontrolled diseases such as lung, kidney and liver infection before enrollment,
9. Women of child-bearing age must undergo a negative pregnancy test (serum or urine) within 7 days prior to enrollment and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last dose; men should agree to contraception during the observation period and within 8 weeks of the last dose,
10. Patients voluntarily participated in this trial and sign the informed consent form,
11. Patients with compliance and expected to follow up the efficacy and adverse reactions as required by the protocol,

Exclusion Criteria:

• 1. Pregnant or lactating women, 2. Patients who need to use systemic steroids at the same time, 3. Under following treatment conditions currently: 1) during the other antitumor clinical observation period within 14 days before blood collection; 2) patient has not recovered from acute side effects of the previous treatment; 4. Receive radiotherapy within 4 weeks before enrollment, 5. Patients who received any other cell therapy before, 6. Patients with unqualified T cell amplification efficiency, 7. Uncontrolled symptoms or other illnesses, including but not limited to infection, congestive heart failure, unstable angina, arrhythmia, psychosis, 8. Patients with severe acute allergic reactions, 9. Patients who have received other cell therapies, 10. Other serious conditions that may limit patient's participation in the study.

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: KD-025; NKG2D-based CAR T-cells Injection; Dosage:1-10x10^6/kg, 70ml/time, The CAR-T cells will be administered by i.v. or hepatic portal artery injection over 20-30 minutes Frequency: total one time	Biological: NKG2D-based CAR T-cells; Autologous genetically modified anti-NKG2DLs CAR transduced T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	The number of patiens who suffered ≥ 3 grade toxicities according to the CTCAE criteria after CAR-T therapy.	through study completion, an average of 3 months.
Detailed adverse events post NKG2D-based CAR-T therapy.	The events included infusion reactions, CRS, tumor lysis syndrome and hematological toxicity. The criteria mainly reffered to guidelines for immune related adverse reactions.	through study completion, an average of 3 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason	2 years post infusion
Progress Free Survival (PFS)	Progress Free Survival after administration	2 years post infusion
Partial response rate	According the RECISE 1.1 criteria, as to the measurable primary lesions, we measure the long and short diameter. As to unmeasurable primary leisons, we measure the measurable metastatic lesions.	through study completion, an average of 3 months.

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: KAEDI
• Investigators: Study Director: kuaile zhao, doctor, Fudan University; Study Director: Changchun Cai, doctor, Xunyang Changchun Shihua Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 20, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 20, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: solid tumors; NKG2D-based CAR T-cells
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Glioblastoma; Medulloblastoma
• Other Study ID Numbers: Fudan-Changchun

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