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TIL Therapy in Metastatic Melanoma and IL2 Dose Assessment (METILDA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01995344
Recruitment Status : Unknown
Verified November 2013 by Professor Robert Hawkins, University of Manchester.
Recruitment status was:  Not yet recruiting
First Posted : November 26, 2013
Last Update Posted : November 26, 2013
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Professor Robert Hawkins, University of Manchester

Tracking Information
First Submitted Date  ICMJE November 21, 2013
First Posted Date  ICMJE November 26, 2013
Last Update Posted Date November 26, 2013
Study Start Date  ICMJE October 2013
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
  • Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 6 weeks post treatment ]
    Subject will have CT scan at 6 weeks post treatment to compare with baseline CT scan in order to assess disease response to therapy
  • Disease response according to RECIST criteria [ Time Frame: 12 weeks post treatment ]
    Subject will have CT scan at 12 weeks post treatment to compare with baseline CT scan in order to assess disease response to therapy
  • Disease response according to RECIST criteria [ Time Frame: 24 weeks post treatment ]
    Subject will have CT scan at 24 weeks post treatment to compare with baseline and previous post-treatment CT scans in order to assess disease response to therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TIL Therapy in Metastatic Melanoma and IL2 Dose Assessment
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Melanoma
Intervention  ICMJE
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Genetic: Tumour Infiltrating Lymphocytes
    Other Name: TIL
  • Drug: Interleukin-2
    Other Name: IL2
Study Arms  ICMJE
  • Active Comparator: 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
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Genetic: Tumour Infiltrating Lymphocytes
    • Drug: Interleukin-2
  • Active Comparator: 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
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Genetic: Tumour Infiltrating Lymphocytes
    • Drug: Interleukin-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 21, 2013)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01995344
Other Study ID Numbers  ICMJE 11_DOG14_12
2013-001071-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Professor Robert Hawkins, University of Manchester
Original Responsible Party Same as current
Current Study Sponsor  ICMJE The Christie NHS Foundation Trust
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Institute for Health Research, United Kingdom
Investigators  ICMJE Not Provided
PRS Account The Christie NHS Foundation Trust
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP