- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02379195
Peginterferon and TIL Therapy for Metastatic Melanoma
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.
Studienübersicht
Status
Bedingungen
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
-
-
Herlev
-
Copenhagen, Herlev, Dänemark, 2730
- Center for Cancer Immune Therapy, Dept. of Haematology/Oncology
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
-
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: 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
Andere Namen:
The maximum number of expanded TILs are infused over 30-45 min on day 0
Andere Namen:
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)
Andere Namen:
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of Participants With Adverse Events/Serious Adverse Events
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Treatment Related Immune Responses
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: 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
- Hauptermittler: Rikke Andersen, MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Neubildungen nach histologischem Typ
- Neubildungen
- Neuroektodermale Tumoren
- Neoplasmen, Keimzelle und Embryonal
- Neubildungen, Nervengewebe
- Neuroendokrine Tumoren
- Nävi und Melanome
- Melanom
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Agenten des peripheren Nervensystems
- Antivirale Mittel
- Analgetika
- Agenten des sensorischen Systems
- Analgetika, nicht narkotisch
- Antirheumatika
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Antineoplastische Mittel, alkylierend
- Alkylierungsmittel
- Myeloablative Agonisten
- Cyclophosphamid
- Fludarabin
- Peginterferon alfa-2b
- Interleukin-2
Andere Studien-ID-Nummern
- MM1413
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .