Adjunctive use of nilotinib in patient with imatinib resistant or intolerant chronic myeloid leukaemia (CML) undergoing a reduced intensity conditioned allogeneic transplant

ISRCTN ISRCTN12974558
DOI https://doi.org/10.1186/ISRCTN12974558
Secondary identifying numbers RG_07-202
Submission date
22/08/2008
Registration date
30/09/2008
Last edited
16/04/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Charles Craddock
Scientific

Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Email charles.craddock@uhb.nhs.uk

Study information

Study designPhase I/II multicentre single-arm open-label non-randomised study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titlePhase I/II study of the adjunctive use of nilotinib in patients undergoing reduced intensity allogeneic transplantation for imatinib resistant or intolerant chronic myeloid leukaemia
Study acronymTRICE
Study objectivesDisease 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(s)Cambridgeshire 1 Research Ethics Committee, 24/10/2008, ref: 08/H0304/91
Health condition(s) or problem(s) studiedChronic myeloid leukaemia (CML)
InterventionNilotinib 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)Nilotinib
Primary outcome measureSafety 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 measures1. Relapse rate, assessed at 12 months post-transplant
2. Survival, assessed annually until 3 years post-transplant
Overall study start date03/11/2008
Completion date29/10/2010

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants15 patients
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment03/11/2008
Date of final enrolment29/10/2010

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Research and Commercial Services
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Email charles.craddock@uhb.nhs.uk
Website http://www.rcs.bham.ac.uk
ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Industry

Novartis Pharmaceuticals UK Limited
Private sector organisation / For-profit companies (industry)
Alternative name(s)
Novartis UK, NOVARTIS UK LIMITED
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

Editorial Notes

16/04/2018: No publications found, verifying study status with principal investigator.
14/03/2016: No publications found, verifying study status with principal investigator