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 |
| Protocol serial number | RG_07-202 |
| Sponsor | University of Birmingham (UK) |
| Funder | Novartis Pharmaceuticals UK Limited |
- 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
Scientific
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
| charles.craddock@uhb.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase I/II multicentre single-arm open-label non-randomised study |
| Secondary study design | Non randomised study |
| Study type | Participant information sheet |
| 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 |
| Study acronym | TRICE |
| Study objectives | 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(s) | Cambridgeshire 1 Research Ethics Committee, 24/10/2008, ref: 08/H0304/91 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Nilotinib |
| Primary outcome measure(s) |
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. |
| Key secondary outcome measure(s) |
1. Relapse rate, assessed at 12 months post-transplant |
| Completion date | 29/10/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 15 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 03/11/2008 |
| Date of final enrolment | 29/10/2010 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not 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 | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
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
