- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
-
-
Herlev
-
Copenhagen, Herlev, Danimarca, 2730
- Center for Cancer Immune Therapy, Dept. of Haematology/Oncology
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
-
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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
Altri nomi:
The maximum number of expanded TILs are infused over 30-45 min on day 0
Altri nomi:
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)
Altri nomi:
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Participants With Adverse Events/Serious Adverse Events
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Treatment Related Immune Responses
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: 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
- Investigatore principale: Rikke Andersen, MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Tumori neuroectodermici
- Neoplasie, cellule germinali ed embrionali
- Neoplasie, tessuto nervoso
- Tumori neuroendocrini
- Nevi e melanomi
- Melanoma
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti del sistema nervoso periferico
- Agenti antivirali
- Analgesici
- Agenti del sistema sensoriale
- Analgesici, non narcotici
- Agenti antireumatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agonisti mieloablativi
- Ciclofosfamide
- Fludarabina
- Peginterferone alfa-2b
- Interleuchina-2
Altri numeri di identificazione dello studio
- MM1413
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .