Konstruerte immuneffekter mot livmorhalskreft
Innovativ behandling av livmorhalskreft ved bruk av konstruerte antigenspesifikke immuneffekter (EIE)
The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.
Studieoversikt
Detaljert beskrivelse
Cervical cancer (CC) is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of the cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, CC is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of CC consists of surgical intervention, radiation, chemotherapy and immunotherapy.
Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of CC-specific engineered immune effectors including cytotoxic T lymphocytes in patients.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
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Guangdong
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Shenzhen, Guangdong, Kina, 518000
- Shenzhen Geno-immune Medical Institute
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
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Written, informed consent obtained prior to any study-specific procedures.
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Age older than 10 years.
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Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
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Expected survival ≥ 12 weeks.
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Not pregnant, and on appropriate birth control if of childbearing potential.
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Evidence of high-risk HPV infection.
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Stage III-IV or recurrent cervical cancer.
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Initial hematopoietic reconstitution with
- neutrophils (ANC) ≥ 1,000/mm^3;
- platelet (PLT) ≥ 100,000/mm^3.
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Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with
- serum creatinine ≤ 2×ULN;
- serum bilirubin ≤ 2×ULN;
- AST/ALT ≤ 2×ULN;
- ALKP ≤ 5×ULN;
- serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.
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Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test negative.
Exclusion Criteria:
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Patients with
- cervical benign lesions: cervical columnar epithelium ectopic, cervical polyps, cervical endometriosis and cervical tuberculous ulcers;
- cervical benign tumors: cervical submucous myoma, cervical cancer, cervical papilloma.
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Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
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Previous exposure to mouse SCC antibody.
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Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
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Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).
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Pregnant or lactating females.
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Inadequate bone marrow function with
- absolute neutrophil count < 1,000/mm^3;
- platelet count < 100,000/mm^3;
- Hb < 9 g/dL.
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Inadequate liver and renal function with
- serum (total) bilirubin > 1.5 x ULN;
- AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases);
- alkaline phosphatase > 2.5 x ULN;
- serum creatinine >2.0 mg/dl (> 177 μmol/L);
- urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
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Serious active infection requiring i.v. antibiotics at during screening.
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Subject actively infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: CC-EIEs
Autologous cervical cancer specific engineered immune effectors (EIEs) |
2 to 4 infusions, once a week, for 1x10^5~1x10^7 CTLs/kg via IV, abdominal cavity or intratumoral injection each time |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Safety of CC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
Tidsramme: 6 months
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Physiological parameter (measuring cytokine response, fever, symptoms) |
6 months
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Anti-tumor effects
Tidsramme: 1 year
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Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. |
1 year
|
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Functional analyses of CC-EIEs in vitro
Tidsramme: 4 weeks
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The specificity of CC-EIEs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT). |
4 weeks
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Lung-Ji Chang, PhD, Shenzhen Geno-Immune Medical Institute
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Urogenitale sykdommer
- Kjønnssykdommer
- Urogenitale neoplasmer
- Neoplasmer etter nettsted
- Neoplasmer
- Kvinnelige urogenitale sykdommer
- Kvinnelige urogenitale sykdommer og graviditetskomplikasjoner
- Livmorsykdommer
- Kjønnssykdommer, kvinner
- Genitale neoplasmer, kvinnelige
- Livmor livmorhalssykdommer
- Uterine neoplasmer
- Uterine cervikale neoplasmer
Andre studie-ID-numre
- GIMI-IRB-17019
Plan for individuelle deltakerdata (IPD)
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