A Cancer Research UK phase I trial of adoptive transfer of autologous tumour antigen specific T-cells with pre-conditioning chemotherapy and intravenous interleukin-2 (IL2) in patients with advanced carcinoembryonic antigen (CEA) positive tumours

ISRCTN	ISRCTN65902492
DOI	https://doi.org/10.1186/ISRCTN65902492
ClinicalTrials.gov (NCT)	NCT01212887
Clinical Trials Information System (CTIS)	2005-004085-16
Protocol serial number	6499
Sponsor	Christie Hospital NHS Foundation Trust (UK)
Funder	Cancer Research UK (CRUK) (UK)

Submission date: 30/06/2010
Registration date: 30/06/2010
Last edited: 06/03/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-mfez-t-cells-chemotherapy-and-il2-for-cancers-that-test-positive-for-carcinoembryonic-antigen

Contact information

Ms Anvi Wadke
Scientific

Department of Medical Oncology
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom

Phone	+44 161 446 8107
Email	anvi.wadke@christie.nhs.uk

Study information

Primary study design	Interventional
Study design	Single centre non-randomised interventional treatment trial
Secondary study design	Non randomised controlled trial
Scientific title	A Cancer Research UK phase I trial of adoptive transfer of autologous tumour antigen specific T-cells with pre-conditioning chemotherapy and intravenous interleukin-2 (IL2) in patients with advanced carcinoembryonic antigen (CEA) positive tumours
Study acronym	MFEz Study
Study objectives	This trial proposes to use engineered T cells (MFEz T cells) comprising polyclonal CD4 and CD8 populations in place of the selected, specific TILs and combines these with 'supportive therapies' of pre-conditioning chemotherapy and high dose intravenous IL2.
Ethics approval(s)	MREC approved (ref: GTAC096)
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: All Cancers/Misc Sites; Disease: All
Intervention	Patients will receive pre-conditioning chemotherapy followed by MFEz T cells and then intravenous IL2. The pre-conditioning chemotherapy regime and the dose of MFEz T cells will be determined by the dose escalation scheme. Chemotherapy will only be commenced if adequate transduction and expansion of MFEz T cells has occurred. One cycle only of chemotherapy and MFEz T cells will be given. Further cycles of IL2 may be considered if specified criteria are met. Study entry: registration only
Intervention type	Other
Primary outcome measure(s)	To evaluate the feasibility of using MFEz T cells
Key secondary outcome measure(s)	1. To determine dose of MFEz T cells that gives the highest frequency in the circulation as measured 2. Adverse event assessment for as long as the patient is able to attend clinic according to CTCAE
Completion date	17/05/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	22
Key inclusion criteria	1. Have histologically confirmed malignancy that is CEA positive that is metastatic or unresectable and for which standard curative or palliative measures: 1.1. Do not exist 1.2. Are no longer effective 1.3. Have been completed 1.4. Have been refused 2. Provide written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up 3. Be 18 years or over, either sex 4. Have a life expectancy of at least 3 months 5. Have a World Health Organization (WHO) performance status of 0 or 1 6. Female patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test prior to enrolment and agree to use appropriate medically approved contraceptive precautions for four weeks prior to leukapheresis, during the trial, and for six months afterwards 7. Male patients must agree to use barrier method contraception during the trial and for six months afterwards 8. Patients receiving cyclophosphamide must have a left ventricular ejection fraction (LVEF) of greater than or equal to 50% on multiple gated acquisition (MUGA) scan (within 4 weeks prior to leukapheresis) 9. Patients must have haematological and biochemical indices within the following ranges at screening. These measurements must be repeated to confirm eligibility between leukapheresis and commencing chemotherapy.
Key exclusion criteria	1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosureas and Mitomycin-C) prior to treatment with chemotherapy in the trial or during the course of the trial. 2. Toxic manifestations of previous treatments. Exceptions to this are alopecia or certain grade 1 toxicities which in the opinion of the Investigator and CRUK should not exclude the patient (grade 1 neuropathy or grade 1 fatigue). 3. Primary brain tumours or brain metastases 4. Major thoracic and/or abdominal surgery from which the patient has not yet recovered 5. At high medical risk because of non-malignant systemic disease including active uncontrolled infection 6. Known to be serologically positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human T cell lymphotropic virus (HTLV) 7. History of autoimmune disease 8. Inflammatory bowel disease 9. Concurrent congestive heart failure or prior history of class III - IV cardiac disease (New York Heart Association [NYHA]) 10. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow 11. Patients who are taking, or likely to require systemic steroids or other immunosuppressive therapy 12. Current malignancies originating from other primary 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 13. Participation in any other clinical trial within the previous 30 days prior to leukapheresis or during the course of this trial 14. Concurrent serious infections within the 28 days prior to leukapheresis 15. Any other condition which in the Investigator's opinion would not make the patient a suitable candidate for the clinical trial
Date of first enrolment	29/11/2007
Date of final enrolment	17/05/2010

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Department of Medical Oncology

Manchester
M20 4BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2017		Yes	No

Editorial Notes

06/03/2018: Publication reference added.