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中国科学家世界首个人类CRISPR基因编辑临床试验详细信息
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中国科学家将进行世界首个人类CRISPR基因编辑临床试验
详细报道 http://news.bioon.com/article/6686143.html?clientAgent=xgb
详细信息 https://clinicaltrials.gov/ct2/show/NCT02793856?term=CRISPR&rank=1
PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer
Purpose| Condition | Intervention | Phase |
|---|---|---|
| Metastatic Non-small Cell Lung Cancer | Drug: Cyclophosphamide Other: PD-1 Knockout T Cells Drug: Interleukin-2 | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Metastatic Non-small Cell Lung Cancer |
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients [ Time Frame: Dose Escalation - Approximately 6 months ] [ Designated as safety issue: Yes ]
Response Rate [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Response will be evaluated according to RECIST v1.1Progression free survival - PFS [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months ] [ Designated as safety issue: No ]
Overall Survival - OS [ Time Frame: The time from randomization to death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
Peripheral blood circulating tumor DNA [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatmentTemporal Interleukin-2 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ] [ Designated as safety issue: No ]
Temporal Interferon-γ change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ] [ Designated as safety issue: No ]
Temporal tumour necrosis factor-α change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ] [ Designated as safety issue: No ]
Temporal Interleukin-6 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 15 |
| Study Start Date: | July 2016 |
| Estimated Study Completion Date: | April 2018 |
| Estimated Primary Completion Date: | April 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: A - Two cycles Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant). Patients will receive a total of two cycles of treatment. | Drug: Cyclophosphamide To deplete Tregs before collecting peripheral blood Other Name: Cytoxan Other: PD-1 Knockout T CellsAutologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment Drug: Interleukin-2Given in the following 5 days at 720,000 international unit（IU）/Kg/day Other Name: IL-2 |
| Experimental: B- Three cycles Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant). Patients will receive a total of three cycles of treatment. | Drug: Cyclophosphamide To deplete Tregs before collecting peripheral blood Other Name: Cytoxan Other: PD-1 Knockout T CellsAutologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment Drug: Interleukin-2Given in the following 5 days at 720,000 international unit（IU）/Kg/day Other Name: IL-2 |
| Experimental: C- Four cycles Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant). Patients will receive a total of four cycles of treatment. | Drug: Cyclophosphamide To deplete Tregs before collecting peripheral blood Other Name: Cytoxan Other: PD-1 Knockout T CellsAutologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment Drug: Interleukin-2Given in the following 5 days at 720,000 international unit（IU）/Kg/day Other Name: IL-2 |
Detailed Description:
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Pathologically verified stage IV non-small cell lung cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)
Progressed after all standard treatment
Performance score: 0-1
Expected life span: >= 6 months
Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
Major organs function normally
Women at pregnant ages should be under contraception
Willing and able to provide informed consent
Exclusion Criteria:
Pathology is mixed type
Emergent treatment of tumor emergency is needed
Poor vasculature
Coagulopathy, or ongoing thrombolytics and/or anticoagulation
Blood-borne infectious disease, e.g. hepatitis B
History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
With other immune diseases, or chronic use of immunosuppressants or steroids
Compliance cannot be expected
Other conditions requiring exclusion deemed by physician
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT02793856
| Contact: You Lu, MD | 0086-28-85423571 | radyoulu@hotmail.com | |
| Contact: Xiaojuan Zhou, MD | 0086-28-85423571 | zhouxiaojuan765@163.com |
| China, Sichuan | |
| West China Hospital, Sichuan University | |
| Chengdu, Sichuan, China, 610041 | |
| Principal Investigator: | You Lu, MD | Sichuan University |
More InformationPublications:
| Responsible Party: | You Lu, Chair of Department of Thoracic Cancer, Sichuan University |
| ClinicalTrials.gov Identifier: | NCT02793856 History of Changes |
| Other Study ID Numbers: | MHC001 |
| Study First Received: | May 30, 2016 |
| Last Updated: | July 12, 2016 |
| Health Authority: | China: Food and Drug Administration |
| Individual Participant Data | |
| Plan to Share IPD: | Undecided |
Keywords provided by Sichuan University:
| lung cancer immune checkpoint PD-1 CRISPER autologous cell infusion |
Additional relevant MeSH terms:
| Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Cyclophosphamide Interleukin-2 Immunosuppressive Agents | Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on July 20, 2016
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