PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer
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| ClinicalTrials.gov Identifier: NCT02793856 |
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Recruitment Status :
Completed
First Posted : June 8, 2016
Results First Posted : December 21, 2020
Last Update Posted : January 12, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Non-small Cell Lung Cancer | Drug: Cyclophosphamide Other: PD-1 Knockout T Cells | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 12 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Clinical Trial of PD-1 Knockout Engineered T Cells Treating Patients With Advanced Non-small Cell Lung Cancer |
| Actual Study Start Date : | August 26, 2016 |
| Actual Primary Completion Date : | August 20, 2018 |
| Actual Study Completion Date : | March 17, 2020 |
| Arm | Intervention/treatment |
|---|---|
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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 1 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. 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 Cells Autologous 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 |
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Experimental: B- 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. 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 Cells Autologous 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 |
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Experimental: C- 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 4 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. 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 Cells Autologous 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 |
- 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 ]
- Number of Patients With Overall Response [ Time Frame: 3 months ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
- Number of Patients With Disease Control at 8 Weeks [ Time Frame: 8 weeks ]Response will be evaluated according to RECIST v1.1 for target lesions at Week 8：Complete Response (CR), Disappearance of all extranodal target lesions; Partial Response (PR) ≥ 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Disease control = CR +PR+SD
- Progression Free Survival (PFS) [ Time Frame: The time from the date of first edited T cell infusion to the date of disease progression or death due to any reason. ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Overall Survival (OS) [ Time Frame: The duration from date of first edited T cell infusion to the date of death due to any reason ]OS is defined as the time interval from date of first edited T cell infusion to the date of death due to any reason
- Number of Participants With Genes Mutations in Peripheral Blood Circulating Tumor DNA (ctDNA) [ Time Frame: Baseline ]Driver genes mutaion stauts of Participants in ctDNA from peripheral blood were assessed by next generation sequencing (NGS), to explore the positive rate of sepicif driver genes (e.g. EGFR, ALK, ROS1, etc.) and the relationship between gene mutation status and clinical response
- Interleukin-6 Change in the Peripheral Blood. [ Time Frame: Baseline, 1 month and 3 month ]Peripheral Interleukin-6 level at different timepoint (Baseline, 1 month and 3 month) was measured using rate nephelometry
- Interleukin-10 Change in the Peripheral Blood. [ Time Frame: Baseline, 1 month and 3 month ]Peripheral Interleukin-10 level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.
- Tumor Necrosis Factor-a Change in the Peripheral Blood. [ Time Frame: Baseline, 1 month and 3 month ]Peripheral Tumor Necrosis Factor-a level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02793856
| China, Sichuan | |
| West China Hospital, Sichuan University | |
| Chengdu, Sichuan, China, 610041 | |
| Principal Investigator: | You Lu, MD | Sichuan University |
Documents provided by You Lu, Sichuan University:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | You Lu, Chair of Department of Thoracic Cancer, Sichuan University |
| ClinicalTrials.gov Identifier: | NCT02793856 |
| Other Study ID Numbers: |
MHC-001 |
| First Posted: | June 8, 2016 Key Record Dates |
| Results First Posted: | December 21, 2020 |
| Last Update Posted: | January 12, 2021 |
| Last Verified: | December 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
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lung cancer immune checkpoint PD-1 CRISPR autologous cell infusion |
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |
Cyclophosphamide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |