A randomised, Phase II study in metastatic melanoma to evaluate the effectiveness of adoptive cellular therapy with Tumour Infiltrating Lymphocytes (TIL) and assessment of High Dose Intereukin-2 versus Low-Dose Interleukin-2.

Phase 1

• Conditions: Malignant Melanoma; MedDRA version: 16.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001071-20-GB
• Lead Sponsor: The Christie NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-09-09
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 90

Inclusion Criteria

Inclusion Criteria for TIL Harvest:
•Patients must have histologically confirmed malignant melanoma of cutaneous origin.
•They must have resectable metastatic lesion(s) of at least 2cm in total diameter.
•They must be likely to fulfil the full criteria for TIL therapy at a future date.
•The must give full written informed consent to the surgical procedure and the TIL harvest/storage.

Inclusion Criteria for TIL Therapy
•Patients must have histologically confirmed malignant melanoma of cutaneous origin with confirmed evidence of progressive metastatic disease and to have failed / refused standard therapies.
•Patients may enter if they have previously had TIL (successfully) harvested and stored at the Manchester Cell Therapy Unit.
•There must be measurable / evaluable disease.
•Patients may have had any previous systemic therapies including anti-CTLA4 (Ipilimumab) agent provided they are otherwise fit for treatment.
•Age equal to or greater than 18 years.
•World Health Organisation (WHO) performance status of 0 or 1.
•Life expectancy >3months.
•LVEF > 50% as measured by ECHO/MUGA and satisfactory stress ECHO (if over 60 or had previous cardiotoxic therapy).
Haematological and biochemical indices:
- Haemoglobin (Hb), = 9.0 g/L
- Neutrophils, = 1.0 x 109/L
- Platelets (Plts), = 100 x 109/L
Any of the following abnormal baseline liver function tests:
serum bilirubin, = 1.5 x ULN
- alanine aminotransferase (ALT) and/or
aspartate aminotransferase (AST) and/or
alkaline phosphatase (ALP) , = 5 x ULN
- Serum creatinine, = 0.15 mmol/L
•Female patients of child-bearing potential must have a negative serum or urine pregnancy test prior treatment and agree to use appropriate medically approved contraceptive precautions for four weeks prior to entering the trial, during the trial and for six months afterwards.
•Male patients must agree to use barrier method contraception during the TIL treatment and for six months afterwards.
•Full written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Exclusions to TIL Harvest are:
•Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
•Previous allogeneic transplant.
•Patient with ocular/mucosal (or any non-cutaneous primary site) melanoma.
•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.
•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.
•Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
•History of systemic autoimmune disease which could be life-threatening if reactivation occurred (for example hypothyroidism would be permissible, prior rheumatoid arthritis or SLE would not).
•Patients who are likely to require long-term systemic steroids or other
•Radiotherapy to >25% skeleton.

Exclusion criteria for TIL Therapy
•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. For patients who had severe colitis (grade 3 / 4) on Ipilimumab (or similar therapy), this must be confirmed as resolved by colonoscopy.
•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/mucosal (or any non-cutaneous primary site) 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.
•Evidence of active infection
•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.
•Patients known or found to be serologically positive for Hepatitis B, C, HIV or HTLV.
•History of systemic autoimmune disease which could be life-threatening if reactivation occurred (for example hypothyroidism would be permissible, prior rheumatoid arthritis or SLE would not).
•Patients with currently more than 3 brain metastases

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified