TIL Therapy in Metastatic Melanoma and IL2 Dose Assessment

NCT01995344 | Terminated Phase 2 DMC

• 2 other identifiers: 11_DOG14_122013-001071-20
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

ARM A: High Dose Interleukin-2 (HD IL2)

ACTIVE COMPARATOR

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; Drug: Interleukin-2

ARM B: Low Dose Interleukin-2 (LD IL2)

ACTIVE COMPARATOR

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; Drug: Interleukin-2

Interventions

Cyclophosphamide DRUG

ARM A: High Dose Interleukin-2 (HD IL2); ARM B: Low Dose Interleukin-2 (LD IL2)

Fludarabine DRUG

ARM A: High Dose Interleukin-2 (HD IL2); ARM B: Low Dose Interleukin-2 (LD IL2)

Tumour Infiltrating Lymphocytes GENETIC

Also known as: TIL

ARM A: High Dose Interleukin-2 (HD IL2); ARM B: Low Dose Interleukin-2 (LD IL2)

Interleukin-2 DRUG

Also known as: IL2

ARM A: High Dose Interleukin-2 (HD IL2); ARM B: Low Dose Interleukin-2 (LD IL2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Paul Lorigan, MD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Robert E Hawkins, MD

  The University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Medical Oncology

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: November 26, 2013
• Study Start: March 1, 2014
• Primary Completion: July 24, 2015
• Study Completion: July 24, 2015
• Last Updated: April 20, 2023

Record last verified: 2023-04

Locations

GB (1)