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.
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Kate Maslen, BSc
- 電話番号：61 8 9224 4503
- メール：kate.maslen@health.wa.gov.au
研究連絡先のバックアップ
- 名前：Peter Lau, MBBS
- メール：peter.lau@perkins.org.au
研究場所
-
-
Western Australia
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Perth、Western Australia、オーストラリア、6000
- Royal Perth Hospital
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コンタクト：
- Kate Maslen, BSc
- 電話番号：0892244503
- メール：kate.maslen@health.wa.gov.au
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コンタクト：
- Ben Carnley, MBBS
- 電話番号：61 8 9224 2244
- メール：benedict.carnley@health.wa.gov.au
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主任研究者：
- Ben Carnley, MBBS
-
副調査官：
- Peter Lau, MBBS
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
他の名前：
Patients will receive up to 6 doses of intravenous aldesleukin (600 000 IU/kg IV) every 8-12 hours post the TIL-ACT infusion.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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
時間枠：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
|
Best objective response rate as per RECIST criteria 1.1
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Median Progression Free Survival
時間枠：From enrolment to 12 months post infusion of Perkileucel
|
Median, calculated as the date between randomisation and the date of documented progression per RECIST 1.1 to month 12 post Perkileucel infusion
|
From enrolment to 12 months post infusion of Perkileucel
|
|
Median Overall Survival
時間枠：From enrolment to 12 months post infusion of Perkileucel
|
Median, calculated by the date from randomisation to 12 months post Perkileucel infusion, or date of death
|
From enrolment to 12 months post infusion of Perkileucel
|
|
Median Progression Free Survival
時間枠：From enrolment to 24 months post Perkileucel infusion
|
Median, calculated as the date between randomisation and the date of documented progression per RECIST 1.1 to month 24 post Perkileucel infusion
|
From enrolment to 24 months post Perkileucel infusion
|
|
Median Overall Survival
時間枠：From enrolment to 24 months post Perkileucel infusion
|
Median, calculated by the date from randomisation to 24 months post Perkileucel infusion, or date of death
|
From enrolment to 24 months post Perkileucel infusion
|
|
Safety Analysis of Perkileucel
時間枠：From enrolment to Day 100 post infusion of Perkileucel
|
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.
|
From enrolment to Day 100 post infusion of Perkileucel
|
協力者と研究者
捜査官
- スタディチェア：Peter Lau, MBBS、Harry Perkins Institute for Medical Research
- 主任研究者：Ben Carnley, MBBS、Royal Perth Hospital
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- U1111-1315-9162
- HREC/114234/PMCC (その他の識別子：Peter MacCallum Cancer Centre Human Research Ethics Committee)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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