Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
30 participants
INTERVENTIONAL
2016-07-31
2025-07-31
Brief Summary
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Detailed Description
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50-100ml blood with be drawn to get enough CD3 T cells at least 2x10\^7. After separation, PBMC will be activated via antibodies of CD3 and CD28 and then transduced by lentivirus bearing the EpCAM CAR gene. Then the EpCAM CAR-T cells will proliferate up to 10-100 folds for infusion. The produced cells will be frozen or infused if available.
Included patients will be preconditioned by cyclophosphamide for lymphodepletion if the levels of white blood cells and lymphocytes are normal. Infusion of T cells, at least 1 day after lymphodepletion, is dose escalating and beginning at the lowest level. If the first level is proven to be safe, the next level will be proceeded. Once severe side effects were observed, the dose will be lowered or the dose will be stopped.
During infusion, patients will be taken care of by cardiogram monitor. Blood drawing will be taken before infusion, at 4h after infusion and on day 4, 7, 14, 30, 60, 90, 120, 150, 180 to determine the presence of CAR-T cells. At the same time, cytokines including IL-6, TNF-alpha and IFN-gamma and C-reactive protein levels will be determined. Routine imaging studies will be proceeded.
To see whether there are long-term side effects of this therapy, patients received CAR-T cells will be followed up to at least 15 years.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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EpCAM CAR-T cells
Autologous T cells from patient are engineered to expressing a special chimeric antigen receptor to recognizing EpCAM by lentiviral vector. The engineered T cells were then endowed cytotoxicity to the tumor cells and hold the potential to inhibit the advance of tumors.
EpCAM CAR-T cells
Patients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed.
Interventions
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EpCAM CAR-T cells
Patients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed.
Eligibility Criteria
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Inclusion Criteria
* Karnofsky score of greater than or equal to 60.
* Informed consent explained to, understood by and signed by subject/guardian. -
* Subject/guardian given copy of informed consent
* Recurrent or refractory EpCAM-positive nasopharyngeal carcinoma, breast cancer, gastric cancer and other epithelial tumors determined by Immunohistochemistry (IHC) or RT-PCR. EpCAM expression in tumors on IHC should be greater than or equal to grade 2 and greater than or equal to 2+ intensity score. Wherein grades are defines as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100% of cell staining for EpCAM and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity.
* Age ≥ 18 years
* Life expectancy ≥ 6 weeks
* Karnofsky score ≥ 60
* Bilirubin less than or equal to 3x normal, AST less than or equal to 5x normal,
* ALT less than or equal to 5x, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 8.0
* Pulse oximetry of greater than or equal to 90% on room air.
* Sexually active subjects must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion. The male partner should use a condom.
* Available autologous transduced T lymphocytes with greater than or equal to 20% expression of EpCAM CAR determined by flow-cytometry and killing of EpCAM-positive targets greater than or equal to 20% in cytotoxicity assay.
* Subjects should have been off other investigational antineoplastic therapy for two weeks prior to entry in this study.
* Cyclophosphamide will be allowed 72 hours preinfusion.
* Dexamethasone up to a total dose of 2 mg per day will be allowed if medically indicated.
* Informed consent explained to, understood by and signed by research subjects/guardian.
* Subject/guardian given copy of informed consent.
Exclusion Criteria
* Severe intercurrent infection.
* Known HIV positivity.
* Pregnant or lactating.
* History of hypersensitivity reactions to murine protein-containing products.
18 Years
65 Years
ALL
No
Sponsors
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Sichuan University
OTHER
Responsible Party
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Wei Wang
Dr
Principal Investigators
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Wei Wang, Ph.D
Role: PRINCIPAL_INVESTIGATOR
State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University
Locations
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West China Hospital, Sichuan University
Chengdu, Sichuan, China
Countries
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References
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Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 2004 Aug 15;64(16):5818-24. doi: 10.1158/0008-5472.CAN-04-0754.
Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jager M, Strohlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007 Jul 1;13(13):3899-905. doi: 10.1158/1078-0432.CCR-06-2769.
Stoecklein NH, Siegmund A, Scheunemann P, Luebke AM, Erbersdobler A, Verde PE, Eisenberger CF, Peiper M, Rehders A, Esch JS, Knoefel WT, Hosch SB. Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker. BMC Cancer. 2006 Jun 23;6:165. doi: 10.1186/1471-2407-6-165.
Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle PA, Mueller-Holzner E, Marth C, Gastl G, Zeimet AG. Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol. 2006 Nov;103(2):483-8. doi: 10.1016/j.ygyno.2006.03.035. Epub 2006 May 6.
Murakami N, Mori T, Yoshimoto S, Ito Y, Kobayashi K, Ken H, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Sumi M, Itami J. Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy. Laryngoscope. 2014 Nov;124(11):E431-6. doi: 10.1002/lary.24839. Epub 2014 Jul 14.
Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015 Jan 31;16(1):1. doi: 10.1186/s12865-014-0064-x.
Other Identifiers
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SKLB-083
Identifier Type: -
Identifier Source: org_study_id