A Randomised Phase II Study in Metastatic Melanoma to Evaluate the Efficacy of Adoptive Cellular Therapy With Tumour Infiltrating Lymphocytes (TIL) and Assessment of High Versus Low Dose Interleukin-2
Overview
- Phase
- Phase 2
- Intervention
- Cyclophosphamide
- Conditions
- Metastatic Melanoma
- Sponsor
- The Christie NHS Foundation Trust
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a two arm, open-labelled phase II randomised trial of Tumour Infiltrating Lymphocytes (TIL) in metastatic melanoma patients given with preconditioning chemotherapy and Interleukin-2 (IL2). Eligible patients will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Patients will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous High Dose Interleukin-2 (HD-IL2) or Low Dose Interleukin-2 (LD-IL2) depending on the randomised arm.
The primary objectives are response rate assessed and compared by CT scans carried out at week 6, week 12 and at 12 weekly intervals thereafter and the evaluation of feasibility and tolerability of TIL therapy with HD-IL2 versus LD-IL2.
Investigators
Christiesponsoredresearch
Professor in Medical Oncology
The Christie NHS Foundation Trust
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed malignant melanoma with confirmed evidence of progressive metastatic disease and to have failed / refused standard therapies.
- •They must have resectable metastatic lesion(s) of at least 2cm in diameter.
- •There must be measurable / evaluable disease after the surgical resection.
- •Patients may have had any previous systemic therapies including anti-CTLA4 (Ipilimumab) agent provided they are otherwise fit for treatment.
- •Tumour samples may be taken prior to other systemic therapy if patients wish to store the sample for possible future use.
- •Age equal to or greater than 18 years.
- •World Health Organisation (WHO) performance status of 0 or
- •Life expectancy \>3months.
- •LVEF \> 50% as measured by ECHO/MUGA and satisfactory stress ECHO (if over 60 or had previous cardiotoxic therapy).
- •Haemoglobin (Hb) ≥ 9.0 g/dL
Exclusion Criteria
- •Those receiving radiotherapy, targeted therapy, immunotherapy, systemic steroids, or chemotherapy during the previous four weeks (six weeks for nitrosoureas and Mitomycin-C) prior to treatment or during the course of the treatment.
- •All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade 1 toxicities, which an investigator considers should not exclude the patient.
- •Previous radiotherapy treatment to the resectable metastatic site(s) within 1 year and no other suitable metastatic sites.
- •Participation in any other clinical trial within the previous 30 days or during the course of this treatment.
- •Previous allogeneic transplant.
- •Patient with ocular melanoma.
- •Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or Class III or IV AHA criteria for heart disease (see Appendix 6)
- •Patients who are high medical risks because of non-malignant systemic disease, including those with, uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which in the lead clinicians opinion would not make the patient a good candidate for this therapy.
- •Concurrent systemic infections (CTCAE Grade 3 or more) within the 28 days prior to treatment.
- •Prior history of malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
Arms & Interventions
ARM A: High Dose Interleukin-2 (HD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous HD IL2
Intervention: Cyclophosphamide
ARM A: High Dose Interleukin-2 (HD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous HD IL2
Intervention: Fludarabine
ARM A: High Dose Interleukin-2 (HD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous HD IL2
Intervention: Tumour Infiltrating Lymphocytes
ARM A: High Dose Interleukin-2 (HD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous HD IL2
Intervention: Interleukin-2
ARM B: Low Dose Interleukin-2 (LD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous LD-IL2
Intervention: Cyclophosphamide
ARM B: Low Dose Interleukin-2 (LD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous LD-IL2
Intervention: Fludarabine
ARM B: Low Dose Interleukin-2 (LD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous LD-IL2
Intervention: Tumour Infiltrating Lymphocytes
ARM B: Low Dose Interleukin-2 (LD IL2)
Eligible participants will undergo surgical tumour excision from which TIL will be derived, cultured and expanded. Participants will receive preconditioning chemotherapy with cyclophosphamide (60mg/kg) day -7 and day -6, followed by fludarabine (25mg/m2) day -5 to day -1. The autologous TILs will be re-infused on day 0 and the patients will receive up to 12 doses of intravenous LD-IL2
Intervention: Interleukin-2
Outcomes
Primary Outcomes
Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Time Frame: Best response
Subject will have CT scan at 6,12,24 weeks post treatment to compare with baseline CT scan in order to assess disease response to therapy