Contact information
Type
Scientific
Primary contact
Prof Charles Craddock
ORCID ID
Contact details
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
-
charles.craddock@uhb.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RG_07-202
Study information
Scientific title
Phase I/II study of the adjunctive use of nilotinib in patients undergoing reduced intensity allogeneic transplantation for imatinib resistant or intolerant chronic myeloid leukaemia
Acronym
TRICE
Study hypothesis
Disease relapse is the major cause of treatment failure after allogeneic transplantation using reduced intensity conditioned (RIC) regimens in patients with chronic myeloid leukaemia (CML) and therefore strategies which reduce the risk of disease relapse are required. Although there has been interest in the use of prophylactic donor lymphocyte infusions (DLI) to reduce the risk of relapse, their use is associated with a significant risk of severe graft-versus-host disease (GvHD) when administered early post-transplant. Nilotinib has potent anti-leukaemic activity in patients who are resistant or intolerant to imatinib and this study aims to examine whether its administration post-transplant can modify the kinetics of disease relapse after a RIC allograft thereby eliminating or postponing the requirement for DLI.
Ethics approval
Cambridgeshire 1 Research Ethics Committee, 24/10/2008, ref: 08/H0304/91
Study design
Phase I/II multicentre single-arm open-label non-randomised study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic myeloid leukaemia (CML)
Intervention
Nilotinib will be commenced on day +35 post-transplant. Nilotinib will be commenced at a dose of 200 mg daily (orally) for two weeks and if this is tolerated, it will be increased to 200 mg twice daily for a further two weeks. Patients will further escalate their dose to 400 mg twice daily (bd) until 12 months post-transplant. Nilotinib will then be discontinued. The total follow-up period is 13 months.
Intervention type
Drug
Phase
Phase I/II
Drug names
Nilotinib
Primary outcome measure
Safety and tolerability of nilotinib therapy. Adverse events and therapy-related side effects will be monitored continuously during nilotinib treatment and until 28 days after the last dose.
Secondary outcome measures
1. Relapse rate, assessed at 12 months post-transplant
2. Survival, assessed annually until 3 years post-transplant
Overall trial start date
03/11/2008
Overall trial end date
29/10/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. BCR/ABL positive CML in first chronic phase
2. Resistant or intolerant to imatinib mesylate
3. Aged greater than 18 years, either sex
4. Patients with a human leukocyte antigen (HLA) identical sibling donor or a suitable matched unrelated donor
5. Patients considered fit for transplantation
6. Patients must be able to swallow capsules
7. Liver function less than 2.5 upper limit of normal
8. In patients with magnesium and potassium levels below the lower limit of normal (LLN), every attempt should be made to normalise levels
9. All men and women of child bearing potential must agree to practice effective contraception during the entire study period
10. CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition or imatinib-resistance or intolerance are eligible
11. Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
12. Be willing and able to comply with the protocol for the duration of the study
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
15 patients
Participant exclusion criteria
1. Patients with an allergy to fludarabine, busulphan, campath or nilotinib
2. BCR/ABL negative CML
3. Pregnant or lactating women
4. Patients with organ allografts
5. Impaired cardiac function
6. Patients with any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial
Recruitment start date
03/11/2008
Recruitment end date
29/10/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Research and Commercial Services
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
charles.craddock@uhb.nhs.uk
Sponsor type
University/education
Website
Funders
Funder type
Industry
Funder name
Novartis Pharmaceuticals UK Limited
Alternative name(s)
Novartis UK
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list