Metastatic Melanoma Clinical Trial
— METILDAOfficial title:
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
Verified date | April 2023 |
Source | The Christie NHS Foundation Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 2 |
Est. completion date | July 24, 2015 |
Est. primary completion date | July 24, 2015 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 1. - 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 - Neutrophils = 1.0 x 109/L - Platelets (Plts) = 100 x 109/L - serum bilirubin = 1.5 x ULN - alanine aminotransferase (ALT) = 5 x ULN - aspartate aminotransferase (AST) = 5 x ULN - 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 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. - 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 more than 3 brain metastases. - Patients with symptomatic brain metastasis measuring more than 10mm in diameter or evidence of significant surrounding oedema on MRI will not be eligible until after treatment demonstrating no clinical or radiologic CNS progression for at least 2 months. Patient must be able to wean off any steroid use 3 weeks before treatment commencement. - Patients who are likely to require long-term systemic steroids or other immunosuppressive therapy. - Pregnant and lactating women. - Radiotherapy to >25% skeleton. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | The Christie NHS Foundation Trust | Manchester | Greater Manchester |
Lead Sponsor | Collaborator |
---|---|
The Christie NHS Foundation Trust | National Institute for Health Research, United Kingdom |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria | 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 | Best response |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT02224781 -
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT05470283 -
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
|
Phase 1 | |
Recruiting |
NCT05388877 -
E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma
|
Phase 1 | |
Active, not recruiting |
NCT05103891 -
Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations
|
Phase 1 | |
Completed |
NCT00414765 -
Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
|
Phase 4 | |
Completed |
NCT02857270 -
A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
|
Phase 1 | |
Completed |
NCT01621490 -
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
|
Phase 1 | |
Recruiting |
NCT05779423 -
Cryoablation+Ipilimumab+Nivolumab in Melanoma
|
Phase 2 | |
Active, not recruiting |
NCT04940299 -
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
|
Phase 2 | |
Active, not recruiting |
NCT02278887 -
Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT02360579 -
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT02521870 -
A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT02177110 -
A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma
|
||
Withdrawn |
NCT01340729 -
Open-Label Study of TPI 287 for Patients With Metastatic Melanoma
|
Phase 1/Phase 2 | |
Withdrawn |
NCT01416844 -
Study of Immune Responses in Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT01468818 -
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00984464 -
Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00631618 -
Clinical Trial of Sutent to Treat Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT00571116 -
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
|
Phase 1 | |
Recruiting |
NCT00226473 -
Standard Palliative Care Versus Standard Palliative Care Plus Polychemotherapy in Metastasized Malignant Melanoma
|
Phase 4 |