ImmuniCell® in Patients With Advanced Cancers

Adaptive Study of the Safety, Tolerability & Efficacy of Autologous γδ T Lymphocyte Therapy (ImmuniCell®) in Patients With Advanced Cancers Refractory to Current Treatment or Have Indolent Disease for Which Immunotherapy May be Beneficial

To determine the safety, tolerability, maximum tolerated dose (MTD) and efficacy of ImmuniCell® in patients with melanoma, renal cell cancer (RCC) or non-small cell lung cancer (NSCLC). The study is an adaptive design that has 3 stages: Stage 1 - dose escalation, Stage 2 - efficacy, and Stage 3 - confirm efficacy in one of the tumor types.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer; Renal Cell Cancer; Malignant Melanoma
• Intervention / Treatment: Biological: ImmuniCell®

Detailed Description

This is an open-label trial of ImmuniCell® treatment of patients with malignant melanoma, renal cell cancer (RCC) or non-small cell lung cancer (NSCLC) which are refractory to current treatment or who have indolent disease for which immunotherapy may be beneficial. The trial is designed to identify a safe dose of ImmuniCell® for future clinical trials, to identify a response signal from one or more of the cancers under investigation and to confirm the safety and efficacy in the selected target tumour.

The trial has three stages:

Stage I comprising a safety cohort of patients to identify a safe dose Stage II comprising an expanded patient group for response signal identification Stage III to confirm efficacy and safety.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Cardiff, United Kingdom
    • Velindre Cancer Centre and University Hospital of Wales
  • Edinburgh, United Kingdom
    • Western General Hospital
  • Glasgow, United Kingdom
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom
    • St. James's University Hospital
  • London, United Kingdom
    • University College London Hospital
  • Oxford, United Kingdom
    • Churchill Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged ≥18 years
2. Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1
3. Subjects with histological or cytological confirmation of advanced malignant melanoma, renal cell carcinoma or NSCLC which are refractory to current standard treatments or who have indolent disease for which immunotherapy may be beneficial
4. Measurable disease according to the irRC criteria

5. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted <2 weeks prior to Cycle 1:

   • Creatinine ≤ 1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance ≥ 50 ml/min
   • Total bilirubin ≤ 1.5 x ULN
   • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN with liver metastases
   • Absolute lymphocyte count ≥1.0 x 10E9/L
   • Absolute Neutrophil Count (ANC) ≥1.5 x 10E9/L
   • Platelets ≥100 x 10E9/L
   • Haemoglobin ≥ 10 g/dL
6. Life expectancy of at least 3 months
7. Suitable increase in starting γδ T cell number to final γδ T cell number in the proliferation assay between 10 days in culture
8. Able to give informed, written consent
9. For female patients and female partners of male patients: must be surgically sterile, postmenopausal, or compliant with two forms of contraception (one of which must be a barrier method) during and for 6 months after the treatment period; female patients must have a negative urine pregnancy test at screening and must not be breast-feeding.

Exclusion Criteria:

1. Other primary cancers apart from non-melanoma skin cancers, carcinoma - in situ of the cervix, or a prior cancer treated with curative intent more than 2 years ago without any evidence or recurrent disease
2. Uncontrolled systemic infection
3. Systemic steroid therapy or other immune-suppressants (except in cases where the patient is receiving treatment with replacement doses for adrenal insufficiency)
4. Treatment with bisphosphonates, for instance zoledronate, in the previous 3 months and throughout the trial
5. New York Heart Association (NYHA) functional class ≥3 or myocardial infarction within 6 months
6. Clinically-significant uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation not requiring therapy.
7. Ulcerative Colitis / Inflammatory bowel disease, Addison's disease
8. Pregnancy or lactation before or during the trial. A urine pregnancy test will be carried out at screening
9. Taking any other investigational medicinal product (IMP) or participation in another interventional clinical trial in the previous 30 days
10. Less than 4 weeks since systemic anti-cancer therapy (tyrosine kinase inhibitors, chemotherapy, immunotherapy, hormonal therapy, radiotherapy) and less than 6 weeks since mitomycin C and nitrosureas
11. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the trial or evaluation of the trial results
12. Any other condition considered by a trial physician to be inappropriate for inclusion to the study such as contraindications to leukapheresis (contraindications to heparin which are: recent cerebral haemorrhage; peptic ulcer; recent surgery to eye or nervous system; hypersensitivity to heparin; past history of Type II heparin induced thrombocytopenia; past history of significant spontaneous haemorrhage; known haemophilia or other bleeding disorder).
13. Serological evidence of active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ImmuniCell®; Subjects will receive 6 cycles of ImmuniCell®, one infusion over an hour, at two-week intervals. During Stage 1, intra-patient dose escalation to achieve a total dose of 30 x 109 γδ T cells.	Biological: ImmuniCell®; Autologous γδ T Lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with drug-related > grade 3 toxicity (except for nausea, vomiting or grade 3 diarrhoea without maximal supportive therapy; anaemia, alopecia, or asymptomatic grade 3 laboratory findings that last for < 7 days)	3 months
Document the clinical response (immediate or delayed CR, PR, SD or PD) of the patients following ImmuniCell® treatment and assess the data for a response signal to guide the confirmatory stage	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in markers of immune response (such as IFN-γ, IL-2 and TNF-α) before the first and subsequent ImmuniCell® infusions	Changes in markers of immune response (such as IFN-γ, IL-2 and TNF-α) before the first and subsequent ImmuniCell® infusions	12 months
Changes in peripheral T lymphocyte counts before the first and subsequent ImmuniCell® infusions (optional)		12 months

Collaborators and Investigators

• Sponsor: TC Biopharm
• Investigators: Principal Investigator: Jeff Evans, Prof., Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): November 27, 2018
• Study Completion (Actual): November 27, 2018

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 29, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Renal Cell; Melanoma
• Other Study ID Numbers: TCB-101-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES