A Phase II Trial of Tumour Infiltrating Lymphocyte Adoptive Cell Therapy in Patients With Immune Checkpoint Inhibitor Resistant Unresectable or Metastatic Melanoma (PERTIL-01)
PERTIL-01: A Phase II Trial of Tumour Infiltrating Lymphocyte Adoptive Cell Therapy in Patients With Immune Checkpoint Inhibitor Resistant Unresectable or Metastatic Melanoma
The goal of this study is to determine the activity of Perkileucel, a tumour infiltrating lymphocyte (TIL) adoptive cell transfer therapy (ACT), in patients with unresectable stage III or metastatic melanoma who have progressed on previous treatment with immune checkpoint inhibitors in the adjuvant or metastatic setting.
Study details:
All participants will receive the investigational treatment, Perkileucel. To create this therapy, participants need to undergo surgical excision of a melanoma lesion to harvest the TILs prior to treatment. Once the TILs have been manufactured, participants will be admitted to hospital to receive 5 days of chemotherapy to prepare their body (lymphodepletion) for the TIL-ACT. Treatment with TIL-ACT will then be given on Day 0 as a single intravenous infusion followed by up to 6 intravenous infusions of high-dose interleukin 2. Blood tests and other assessments will be performed regularly to monitor safety and response.
The total duration of the study is 8 years. Safety will be assessed throughout the full duration of the study. Patients will be monitored for delayed adverse events.
This study will show whether Perkileucel can help control melanoma that has not responded to other treatments and demonstrate feasibility of manufacture and delivery of this treatment in an Australian healthcare setting.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
This is a single arm, open label phase II study to determine the activity of Perkileucel, a tumour infiltrating lymphocyte (TIL) adoptive cell transfer therapy (ACT), in patients with unresectable stage III or metastatic melanoma who have progressed on previous treatment with immune checkpoint inhibitors in the adjuvant or metastatic setting.
Patients with sufficient and accessible tumour tissue measuring at least 1.5 cm will undergo surgical excision. Harvested tumour tissue will be cultured at CTTWA and TIL will be expanded within 5 weeks.
Five days prior to infusion of TIL-ACT, patients will receive a nonmyeloablative lymphodepleting regimen with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m^2) IV once daily for 2 days followed by fludarabine (25mg/m^2) once daily for 3 days.
Patients will then receive a single dose of TIL-ACT of 1 × 10^9 to 2 × 10^11 TIL intravenously on Day 0. Patients will receive up to 6 doses of intravenous high-dose interleukin-2 (600 000 IU/kg IV) every 8-12 hours.
The total inpatient stay from chemotherapy to recovery after IL-2 will be approximately 15 days.
Blood tests and imaging assessments will be performed regularly to monitor safety and response.
The total duration of the study is 8 years. Safety will be assessed throughout the full duration of the study. Patients will be monitored for delayed adverse events.
The assessment of the activity of TIL ACT in patients unresectable or metastatic melanoma resistant to anti-PD1 will be performed using best objective response rate as per RECIST criteria 1.1.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Kate Maslen, BSc
- Número de teléfono: 61 8 9224 4503
- Correo electrónico: kate.maslen@health.wa.gov.au
Copia de seguridad de contactos de estudio
- Nombre: Peter Lau, MBBS
- Correo electrónico: peter.lau@perkins.org.au
Ubicaciones de estudio
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Western Australia
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Perth, Western Australia, Australia, 6000
- Royal Perth Hospital
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Contacto:
- Kate Maslen, BSc
- Número de teléfono: 0892244503
- Correo electrónico: kate.maslen@health.wa.gov.au
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Contacto:
- Ben Carnley, MBBS
- Número de teléfono: 61 8 9224 2244
- Correo electrónico: benedict.carnley@health.wa.gov.au
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Investigador principal:
- Ben Carnley, MBBS
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Sub-Investigador:
- Peter Lau, MBBS
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Adult patients = 18 years = 70 years of age.
- ECOG 0-1 (Appendix A: Eastern Cooperative Oncology Group Performance Status Scale) with an estimated life expectancy of > 6 months
- Histologically confirmed unresectable or stage IV melanoma as per AJCC 8th edition. Unresectable melanoma is defined where the lesions are deemed to be unresectable by the treating surgeon.
- Metastatic melanoma with at least 1 surgically accessible metastatic lesion (or aggregate lesions) with an estimated minimum diameter of = 1.5 cm
- Measurable disease per RECIST 1.1 criteria (in addition to the resected lesion).
- At least one anti-PD1 containing line of systemic therapy for unresectable or metastatic melanoma. Alternatively, one prior line of an adjuvant or neoadjuvant anti-PD1 containing regimen and all related adverse events have either returned to baseline or stabilized.
Exclusion Criteria:
- Life expectancy of less than 3 months.
- Metastatic uveal melanoma.
- Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs (e.g. mycophenolate, infliximab, or others) within the last 3 weeks prior to patient screening. Participants receiving steroids as replacement therapy for adrenocortical insufficiency at =10 mg/day of prednisone or another steroid equivalent dose are acceptable.
Participant has symptomatic untreated brain metastases.
- A participant with historically treated brain metastases (ie, treatment was completed >60 days prior to consenting for study participation) may be considered for study participation if the participant is clinically and radiologically stable for = 60 days
- Participants with previously known asymptomatic brain metastases who do not clinically require treatment may be enrolled.
- More than three melanoma brain metastases or evidence of leptomeningeal disease
Other protocol defined exclusion criteria could apply.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Tumour infiltrating lymphocytes adoptive cell therapy (TIL-ACT)
Patients with sufficient and accessible tumour tissue measuring at least 1.5 cm will undergo surgical excision. Harvested tumour tissue will be cultured at CTTWA and TILs will be expanded within 5 weeks. Five days prior to infusion of TIL-ACT, patients will receive a nonmyeloablative lymphodepleting regimen with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m^2) IV once daily for 2 days followed by fludarabine (25mg/m^2) once daily for 3 days. Patients will then receive 1 × 10^9 to 2 × 10^11 TILs intravenously on Day 1. Patients will receive up to 6 doses of intravenous IL-2 (600 000 IU/kg IV) every 8-12 hours post infusion of the TILs |
TILs are autologous melanoma reactive cells, that are harvested from patient's own melanoma tissue.
Patients will receive the TIL-ACT by a single intravenous infusion on Day 0 at of dose of 5 x 10^9 to 2 x 10^11 TILs.
Five days prior to infusion of TIL-ACT, patients will receive a lymphodepleting chemotherapy with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m^2) IV once daily for 2 days followed by fludarabine (25mg/m^2) once daily for 3 days.
Otros nombres:
Patients will receive up to 6 doses of intravenous aldesleukin (600 000 IU/kg IV) every 8-12 hours post the TIL-ACT infusion.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Assess the activity of TIL ACT in patients unresectable or metastatic melanoma resistant to anti-PD1 using objective response rate as per RECIST 1.1
Periodo de tiempo: From enrolment to 6 months, date of documented progression per RECIST criteria 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first
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Best objective response rate as per RECIST criteria 1.1
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From enrolment to 6 months, date of documented progression per RECIST criteria 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Median Progression Free Survival
Periodo de tiempo: From enrolment to 12 months post infusion of Perkileucel
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Median, calculated as the date between randomisation and the date of documented progression per RECIST 1.1 to month 12 post Perkileucel infusion
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From enrolment to 12 months post infusion of Perkileucel
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Median Overall Survival
Periodo de tiempo: From enrolment to 12 months post infusion of Perkileucel
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Median, calculated by the date from randomisation to 12 months post Perkileucel infusion, or date of death
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From enrolment to 12 months post infusion of Perkileucel
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Median Progression Free Survival
Periodo de tiempo: From enrolment to 24 months post Perkileucel infusion
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Median, calculated as the date between randomisation and the date of documented progression per RECIST 1.1 to month 24 post Perkileucel infusion
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From enrolment to 24 months post Perkileucel infusion
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Median Overall Survival
Periodo de tiempo: From enrolment to 24 months post Perkileucel infusion
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Median, calculated by the date from randomisation to 24 months post Perkileucel infusion, or date of death
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From enrolment to 24 months post Perkileucel infusion
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Safety Analysis of Perkileucel
Periodo de tiempo: From enrolment to Day 100 post infusion of Perkileucel
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Safety analyses will be performed in all treated patients.
Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 by treatment group.
All on-study AEs, treatment-related AEs, SAEs and treatment-related SAEs will be tabulated using worst grade per NCI CTCAE v6.0 criteria by system organ class and preferred term.
On-study lab parameters including haematology, chemistry, liver function, and renal function will be summarised using worst grade NCI CTCAE v6.0 criteria.
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From enrolment to Day 100 post infusion of Perkileucel
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Peter Lau, MBBS, Harry Perkins Institute for Medical Research
- Investigador principal: Ben Carnley, MBBS, Royal Perth Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Neoplasias por tipo histológico
- Enfermedades de la piel
- Tumores neuroectodérmicos
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Tumores neuroendocrinos
- Nevos y Melanomas
- Neoplasias De La Piel
- Enfermedades de la piel y del tejido conectivo
- Melanoma
- Péptidos
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Hidrocarburos
- Factores biológicos
- Mostaza de fosforamida
- Compuestos de mostaza de nitrógeno
- Compuestos de mostaza
- Hidrocarburos, halogenados
- Fosforamidas
- Compuestos organofosforados
- Péptidos de señalización intercelular y proteínas
- Citocinas
- Interleucina
- Linfocinas
- Ciclofosfamida
- Interleucina-2
- aldesleucina
Otros números de identificación del estudio
- U1111-1315-9162
- HREC/114234/PMCC (Otro identificador: Peter MacCallum Cancer Centre Human Research Ethics Committee)
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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