Ignite Creation Date:
2025-12-24 @ 9:35 PM
Ignite Modification Date:
2026-03-24 @ 1:57 PM
Study NCT ID:
NCT02867332
Status:
WITHDRAWN
Last Update Posted:
2019-03-06
First Post:
2016-08-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}], 'ancestors': [{'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D007376', 'term': 'Interleukin-2'}], 'ancestors': [{'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D007378', 'term': 'Interleukins'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D008222', 'term': 'Lymphokines'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'No funding', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2016-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-08', 'completionDateStruct': {'date': '2020-11', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-03-04', 'studyFirstSubmitDate': '2016-08-11', 'studyFirstSubmitQcDate': '2016-08-11', 'lastUpdatePostDateStruct': {'date': '2019-03-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-08-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-11', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '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', 'timeFrame': 'Dose Escalation - Approximately 6 months'}], 'secondaryOutcomes': [{'measure': 'Response Rate:Response will be evaluated according to RECIST v1.1', 'timeFrame': '90 days'}, {'measure': 'Progression free survival - PFS', 'timeFrame': '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'}, {'measure': 'Overall Survival - OS', 'timeFrame': 'The time from randomization to death from any cause, assessed up to 2 years'}, {'measure': 'Peripheral blood circulating tumor DNA', 'timeFrame': '6 weeks'}, {'measure': 'Temporal Interleukin-2 change in the peripheral blood', 'timeFrame': 'Baseline and 1 month and 3 months'}, {'measure': 'Temporal Interferon-γ change in the peripheral blood', 'timeFrame': 'Baseline and 1 month and 3 months'}, {'measure': 'Temporal Interleukin-6 change in the peripheral blood', 'timeFrame': 'Baseline and 1 month and 3 months'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Metastatic Renal Cell Carcinoma']}, 'referencesModule': {'references': [{'pmid': '26895815', 'type': 'BACKGROUND', 'citation': 'Gandini S, Massi D, Mandala M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016 Apr;100:88-98. doi: 10.1016/j.critrevonc.2016.02.001. Epub 2016 Feb 10.'}, {'pmid': '27112171', 'type': 'RESULT', 'citation': 'Koshkin VS, Rini BI. Emerging therapeutics in refractory renal cell carcinoma. Expert Opin Pharmacother. 2016 Jun;17(9):1225-32. doi: 10.1080/14656566.2016.1182987. Epub 2016 May 23.'}, {'pmid': '27085692', 'type': 'RESULT', 'citation': 'Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, Schmidgen MI, Gutzmer R, Utikal JS, Goppner D, Hassel JC, Meier F, Tietze JK, Thomas I, Weishaupt C, Leverkus M, Wahl R, Dietrich U, Garbe C, Kirchberger MC, Eigentler T, Berking C, Gesierich A, Krackhardt AM, Schadendorf D, Schuler G, Dummer R, Heinzerling LM. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun;60:190-209. doi: 10.1016/j.ejca.2016.02.025. Epub 2016 Apr 13.'}, {'pmid': '24504486', 'type': 'RESULT', 'citation': 'Gunturi A, McDermott DF. Potential of new therapies like anti-PD1 in kidney cancer. Curr Treat Options Oncol. 2014 Mar;15(1):137-46. doi: 10.1007/s11864-013-0268-y.'}, {'pmid': '23586712', 'type': 'RESULT', 'citation': 'Bockorny B, Dasanu CA. Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches. Expert Opin Biol Ther. 2013 Jun;13(6):911-25. doi: 10.1517/14712598.2013.778970. Epub 2013 Apr 16.'}, {'pmid': '27641687', 'type': 'DERIVED', 'citation': 'Yi L, Li J. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta. 2016 Dec;1866(2):197-207. doi: 10.1016/j.bbcan.2016.09.002. Epub 2016 Sep 15.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced renal cancer. Blood samples will also be collected for research purposes.', 'detailedDescription': 'This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Pathologically verified stage IV Renal 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)\n* Progressed after all standard treatment\n* Performance score: 0-1\n* Expected life span: \\>= 6 months\n* Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy\n* Major organs function normally\n* Women at pregnant ages should be under contraception\n* Willing and able to provide informed consent\n\nExclusion Criteria:\n\n* Pathology is mixed type\n* Emergent treatment of tumor emergency is needed\n* Poor vasculature\n* Coagulopathy, or ongoing thrombolytics and/or anticoagulation\n* Blood-borne infectious disease, e.g. hepatitis B\n* History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician\n* With other immune diseases, or chronic use of immunosuppressants or steroids\n* Compliance cannot be expected\n* Other conditions requiring exclusion deemed by physician'}, 'identificationModule': {'nctId': 'NCT02867332', 'briefTitle': 'PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma.', 'organization': {'class': 'OTHER', 'fullName': 'Peking University'}, 'officialTitle': 'A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Metastatic Renal Cell Carcinoma', 'orgStudyIdInfo': {'id': '11007965940'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Test group', 'description': '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 2, 3, 4 cycles of treatment.', 'interventionNames': ['Biological: PD-1 Knockout T Cells', 'Drug: Cyclophosphamide', 'Drug: IL-2']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Comparable group', 'description': 'Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will not be knocked out by CRISPR Cas9 in the laboratory (PD-1 Wild-type 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.\n\nA 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 2, 3, 4 cycles of treatment.', 'interventionNames': ['Drug: Cyclophosphamide', 'Drug: IL-2']}], 'interventions': [{'name': 'PD-1 Knockout T Cells', 'type': 'BIOLOGICAL', 'description': 'PD-1 Knockout T Cells and PD-1 wild-type T Cells will be made by Cell Biotech Co., Ltd. 2x107/kg T cells will be used for test group and comparable group separately.', 'armGroupLabels': ['Test group']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'otherNames': ['cytophosphane'], 'description': 'Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.\n\nInterleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant).', 'armGroupLabels': ['Comparable group', 'Test group']}, {'name': 'IL-2', 'type': 'DRUG', 'otherNames': ['Interleukin-2 (IL-2)'], 'description': 'Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit（IU）/Kg/ day (if tolerant).', 'armGroupLabels': ['Comparable group', 'Test group']}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'plan to do'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Peking University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Wujiang Liu', 'investigatorAffiliation': 'Peking University'}}}}