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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2013 by Christie Hospital NHS Foundation Trust
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Professor Robert Hawkins, University of Manchester
ClinicalTrials.gov Identifier:
NCT01995344
First received: November 21, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Metastatic Melanoma
Drug: Cyclophosphamide
Drug: Fludarabine
Genetic: Tumour Infiltrating Lymphocytes
Drug: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Christie Hospital NHS Foundation Trust:

Primary Outcome Measures:
  • Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 6 weeks post treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 90
Study Start Date: October 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Cyclophosphamide Drug: Fludarabine Genetic: Tumour Infiltrating Lymphocytes
Other Name: TIL
Drug: Interleukin-2
Other Name: IL2
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
Drug: Cyclophosphamide Drug: Fludarabine Genetic: Tumour Infiltrating Lymphocytes
Other Name: TIL
Drug: Interleukin-2
Other Name: IL2

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995344

Locations
United Kingdom
The Christie NHS Foundation Trust
Manchester, Greater Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Christie Hospital NHS Foundation Trust
National Institute for Health Research, United Kingdom
  More Information

No publications provided

Responsible Party: Professor Robert Hawkins, Professor in Medical Oncology, University of Manchester
ClinicalTrials.gov Identifier: NCT01995344     History of Changes
Other Study ID Numbers: 11_DOG14_12, 2013-001071-20
Study First Received: November 21, 2013
Last Updated: November 21, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Interleukin-2
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 20, 2014