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Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma (MARVSmALo)

20. januar 2022 oppdatert av: Gary Doolittle

Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma

The researchers will investigate if modified T-cells from a patients own system can be utilized to find and destroy metastatic melanoma tumor and thus improve patient outcomes.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.

The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.

The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.

Studietype

Intervensjonell

Registrering (Faktiske)

7

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Kansas
      • Fairway, Kansas, Forente stater, 66205
        • KU Cancer Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 66 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
  • Life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2

  • Laboratory Values

    • absolute neutrophil count > 500 microliters (mcL)
    • platelet > 50,000 mcL
    • serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal (IULN)
    • total bilirubin < 3 x IULN
    • serum creatinine < 3 x IULN
  • Pulse oximetry of > 95% on room air.
  • Must have recovered from the toxic effects of all prior chemotherapy

Exclusion Criteria:

  • Patients with rapidly progressive disease.
  • Patient is currently receiving any investigational drugs
  • Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
  • Patients must not have tumor in a location where enlargement could cause airway obstruction
  • Patient is pregnant or lactating
  • History of hypersensitivity reactions to murine protein-containing products.
  • Currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporin
  • Received any tumor vaccines within previous six weeks
  • Known hypersensitivity to rat monoclonal antibodies
  • History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus, Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).
  • Allergy to baker's yeast or other components of the vaccines.
  • History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B
  • History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a cause other than the vaccine was indicated.
  • Melanoma involvement of the central nervous system
  • Chemotherapy given within the last 28 days
  • Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

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: tvs-CTL Vaccine
Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.
Biologisk: tvs-CTL Vaccine
autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
Tidsramme: 4 weeks
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
4 weeks
PCR measurement of retroviral construct to measure persistence of infused T-cells
Tidsramme: 4 weeks
To evaluate how long the infused T-cells remain in the blood stream
4 weeks
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
Tidsramme: 4 weeks
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
4 weeks

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
PCR measurement of retroviral construct to measure the expansion of infused T-cells
Tidsramme: 12 months
To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
12 months
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
Tidsramme: 12 months
To compare the frequency of tvs-CTL in the peripheral blood, after revaccination, to the frequency noted in the prior study of autologous activated, CAR-transduced T-cells infused in patients with relapsed, refractory Stage IV melanoma
12 months
Imaging studies to measure tumor response
Tidsramme: 10 weeks
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.
10 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Gary Doolittle

Etterforskere

  • Hovedetterforsker: Gary Doolittle, MD, University of Kansas Medical Center

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

6. oktober 2016

Primær fullføring (Faktiske)

10. oktober 2019

Studiet fullført (Faktiske)

13. september 2021

Datoer for studieregistrering

Først innsendt

18. juni 2015

Først innsendt som oppfylte QC-kriteriene

23. juni 2015

Først lagt ut (Anslag)

26. juni 2015

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

4. februar 2022

Siste oppdatering sendt inn som oppfylte QC-kriteriene

20. januar 2022

Sist bekreftet

1. november 2021

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • Mel-2012-01-01

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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