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| Name | Class |
|---|---|
| KAEDI | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KD-025 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NKG2D-based CAR T-cells | Biological | Autologous genetically modified anti-NKG2DLs CAR transduced T cells |
|
| 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. |
| 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) |
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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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hui Xu | Contact | 13337719185 | huixu1989@163.com | |
| Jiaying Deng, doctor | Contact | 18017312829 | dengjiaying3@sina.com |
| Name | Affiliation | Role |
|---|---|---|
| kuaile zhao, doctor | Fudan University | Study Director |
| Changchun Cai, doctor | Xunyang Changchun Shihua Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xunyang Changchun Shihua Hospital | Recruiting | Jiujiang | Jiangxi | 332000 | China |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D005909 | Glioblastoma |
| D008527 | Medulloblastoma |
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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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. |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
| D018242 | Neuroectodermal Tumors, Primitive |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |