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Peginterferon and TIL Therapy for Metastatic Melanoma

13. januar 2020 opdateret af: Inge Marie Svane

T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma

Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo.

In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.

Studieoversigt

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

12

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Herlev
      • Copenhagen, Herlev, Danmark, 2730
        • Center for Cancer Immune Therapy, Dept. of Haematology/Oncology

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

Histologically confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection

ECOG performance status 0-1

Life expectancy ≥ 3 months

No significant toxicity from prior treatments

Adequate renal, hepatic and hematologic function

Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion af treatment.

Able to comprehend the information given and willing to sign informed consent

-

Exclusion Criteria:

Other Malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.

Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision.

Patients with ocular melanoma

Severe allergies, history of anaphylaxis or known allergies to the administered drugs.

Serious medical or psychiatric comorbidity

Creatinine clearance < 70 ml/min

Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis

Severe and active autoimmune disease

Pregnant and nursing women

Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate

Concomitant treatment with other experimental drugs

Patients with uncontrolled hypercalcemia

Less than four weeks since prior systemic antineoplastic treatment at the time of treatment.

-

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: A

All patients receive the same treatment.

All patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.

The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) on day -7 to day -1.

The TILs are infused on day 0 and Interleukin-2 therapy are administered on day 0 to day 5.

Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days

Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)

Cyclophosphamide 60 mg/kg are administered i.v on day -7 and -6
Fludarabine 25 mg/m2 are administered i.v on day -5 to -1
Andre navne:
  • Fludara
  • Fludarabinphosphat
The maximum number of expanded TILs are infused over 30-45 min on day 0
Andre navne:
  • T-celle infusion
Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Andre navne:
  • Proleukin
  • IL-2
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
Andre navne:
  • PegIntron

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Adverse Events/Serious Adverse Events
Tidsramme: 0-24 weeks
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
0-24 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Treatment Related Immune Responses
Tidsramme: Up to 12 months
Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.
Up to 12 months
Objective Response Rate
Tidsramme: Up to 36 months
Clinical responses will be evaluated by RECIST 1.1 (Response Criteria In Solid Tumors Criteria version 1.1) and assessed by CT scan. Complete response (CR), disapperance of all lesions; Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR
Up to 36 months
Overall Survival
Tidsramme: Up to 36 months
Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method
Up to 36 months
Progression Free Survival
Tidsramme: Up to 36 months
Progression free survival (PFS), defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with the Kaplan Meier method.
Up to 36 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Studieleder: Inge Marie Svane, Prof, PhD, MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
  • Ledende efterforsker: Rikke Andersen, MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. november 2014

Primær færdiggørelse (Faktiske)

1. januar 2018

Studieafslutning (Faktiske)

1. oktober 2018

Datoer for studieregistrering

Først indsendt

27. februar 2015

Først indsendt, der opfyldte QC-kriterier

27. februar 2015

Først opslået (Skøn)

4. marts 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. januar 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

13. januar 2020

Sidst verificeret

1. januar 2020

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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