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

Primary Purpose

Hepatocellular Carcinoma, Glioblastoma, Medulloblastoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
NKG2D-based CAR T-cells
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring NKG2D-based CAR T-cells, solid tumors

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Xunyang Changchun Shihua HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

KD-025

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
Progress Free Survival (PFS)
Progress Free Survival after administration
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.

Full Information

First Posted
November 5, 2021
Last Updated
November 20, 2021
Sponsor
Fudan University
Collaborators
KAEDI
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1. Study Identification

Unique Protocol Identification Number
NCT05131763
Brief Title
NKG2D-based CAR T-cells Immunotherapy for Patient With r/r NKG2DL+ Solid Tumors
Official Title
A Phase I Clinical Trial of NKG2D-based CAR T-cells Injection for Subjects With Relapsed/Refractory NKG2DL+ Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
December 1, 2022 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fudan University
Collaborators
KAEDI

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Glioblastoma, Medulloblastoma, Colon Cancer
Keywords
NKG2D-based CAR T-cells, solid tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
KD-025
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
NKG2D-based CAR T-cells
Intervention Description
Autologous genetically modified anti-NKG2DLs CAR transduced T cells
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
The number of patiens who suffered ≥ 3 grade toxicities according to the CTCAE criteria after CAR-T therapy.
Time Frame
through study completion, an average of 3 months.
Title
Detailed adverse events post NKG2D-based CAR-T therapy.
Description
The events included infusion reactions, CRS, tumor lysis syndrome and hematological toxicity. The criteria mainly reffered to guidelines for immune related adverse reactions.
Time Frame
through study completion, an average of 3 months.
Secondary Outcome Measure Information:
Title
overall survival (OS)
Description
For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason
Time Frame
2 years post infusion
Title
Progress Free Survival (PFS)
Description
Progress Free Survival after administration
Time Frame
2 years post infusion
Title
Partial response rate
Description
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.
Time Frame
through study completion, an average of 3 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men or women≥18 years old, Patient with NKG2DL+ cell tumors confirmed by pathology and histology, Fail or unwilling to receive first-line treatment, Disease must be measurable according to the corresponding guidelines, 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 Expected survival time ≥3 months, Patient with adequate bone marrow reserve, hepatic and renal functions, No other uncontrolled diseases such as lung, kidney and liver infection before enrollment, 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, Patients voluntarily participated in this trial and sign the informed consent form, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Xu
Phone
13337719185
Email
huixu1989@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jiaying Deng, doctor
Phone
18017312829
Email
dengjiaying3@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
kuaile zhao, doctor
Organizational Affiliation
Fudan University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Changchun Cai, doctor
Organizational Affiliation
Xunyang Changchun Shihua Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Xunyang Changchun Shihua Hospital
City
Jiujiang
State/Province
Jiangxi
ZIP/Postal Code
332000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Changchun Cai, doctor
Phone
13870257887
Email
m13870257887@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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

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