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| The clinical effectiveness and cost-effectiveness of imatinib in the treatment of chronic myeloid leukaemia |
| Source of record | National Research Register |
| Serial number at source | N0484104355 |
| Project title | The clinical effectiveness and cost-effectiveness of imatinib in the treatment of chronic myeloid leukaemia |
| Current status of trial | Complete |
| Main research question | What is the effectiveness and cost effectiveness of Imatinib (STI 571) in the treatment of chronic myeloid leukaemia? Chronic myeloid leukaemia (CML) is a clonal disorder in which haemopoetiic stem cells proliferate and eventually replace all normal bone marrow function. Median age at diagnosis is 67 years. The disease generally passes through three phases – a chronic stage in which patients usually present, and which lasts typically between 2 and 6 years; an accelerated stage where the number of blast cells in the blood increases and symptoms become more prominent; and a blastic stage when there is little remaining normal marrow function. Median survival is between 4 and 5 years from diagnosis. Bone marrow transplantation is the only potential cure. It is possible in those patients for whom a suitable donor is available, preferably a tissue-type identical sibling, but matched unrelated donors can be used. Survival is between 60 and 70% at 5 years for sibling donors, less for unmatched donors. Bone marrow transplantation is not usually offered to patients older than 60 because of the increased risks of the procedure in older patients. Drug treatments ameliorate symptoms and prolong overall survival. Hydroxyurea is the usual initial treatment and has relatively few side effects. Busulphan is now rarely used because of its unfavourable side effects and apparent lower efficacy. Interferon alpha has become increasingly used in the last few years as it prolongs survival by between 1 and 2 years. However, it also has significant toxic effects, which requires a reduction in dose or cessation of therapy in a substantial proportion of patients. Cytosine therapy in combination with interferon increases the likelihood of remission at the expense of increased toxicity. CML has a characteristic genetic abnormality of chromosomes 9 and 22 (known as Philadelphia Chromosome). A protein known as BCR-ABL is produced as a result of this, and the enzyme activity of the protein (tyrosine kinase) appears to be implicated in the development of CML. Imatinib has been synthesised specifically to be an antagonist of this tyrosine kinase. It has a limited effect on other, normal, kinases. Antileukaemic activity has been demonstrated in a number of preclinical and animal models. Preliminary review of the literature reveals that two phase I studies have been published in peer reviewed journals, reporting on 121 patients with CML. Three phase II studies have been conducted, one in the chronic stage for patients who are resistant or refractory to interferon alfa, one in the accelerated stage, and one in the blast stage of CML. These studies have been published in abstract only. Effectiveness was evaluated on the basis of haematological or cytogenetic response. Duration of response has not been estimated because of short follow up, however, these studies are ongoing. A randomised controlled trial comparing imatininb with interferon alpha and cytosine arabinoside has closed recruitment. The primary outcome measure is time to progression of one of a number of endpoints including loss of haematological remission, loss of cytogenetic remission, progression to accelerated or blast phase, or death from CML. The first year report will not be available until the first quarter of 2002, with the final report not expected until 2005. Adverse effects have been reported in the literature but no information on quality of life appears to be available. No published cost data has been identified so far. There is little data on children, at least partly because CML is very rare in this age group. Scope: This review will encompass the efficacy of Imatinib in all stages of CML. Population: All adults enrolled in trials with CML, in chronic, accelerated or blast stage. Interventions to be considered: As there is a paucity of published information, rigorous assessment of effectiveness and cost effectiveness is deemed unlikely to be achievable. Inferences derived from Phase I and II studies do not provide good evidence of effectiveness. Therefore the interventions to be considered are: 1. The efficacy of Imatinib in chronic myeloid leukaemia that is resistant, intolerant of or refractory to alpha interferon. 2. The efficacy of Imatinib in chronic myeloid leukaemia in accelerated phase. 3. The efficacy of Imatinib in chronic myeloid leukaemia in blast crisis. 4. The safety of Imatinib in chronic myeloid leukaemia of all stages. 5. The cost of Imatinib in chronic myeloid leukemia. It is possible that the industry submission will include unpublished information from randomised controlled trials. Depending on the extensiveness of the information contained in the submission, if possible, we will assess effectiveness and cost-effectiveness, against comparators of standard treatment (hydroxyurea, alpha interferon and bone marrow transplantation). Outcomes to be considered: 1. Progression-free survival (if available). 2. Overall survival (if available). 3. Haematological response, complete and partial. 4. Cytogenic response, complete and partial. 5. Adverse effects including nausea, diarrhoea, myalgia, perorbital oedemia, skin rash, peripheral oedema, liver toxicity, withdrawal from treatment, myelosuppression and cytopaenia). 6. Cost. It will not be possible to rigorously assess the optimal duration of treatment, or quality of life. However, if information on these factors is identified during the searching process, a summary and critique of the evidence will be provided National Institute of Clinical Excellence. Details of the appraisal timetable and process can be found at the |
| Design/methodology | Technology Assessment Review |
| Multi-centre trial? | This is not a multi-centre trial. |
| Start date | 08/22/2001 |
| End date | 02/21/2002 |
| Primary keywords | QUALITY-OF-LIFE; LEUKEMIA-MYELOID-CHRONIC Q-drug-therapy; CGP-57148 Q-therapeutic-use; ANTINEOPLASTIC-AGENTS Q-therapeutic-use |
| Secondary keywords | HUMAN; RANDOMIZED-CONTROLLED-TRIAL; CLINICAL-TRIAL; SURVIVAL-ANALYSIS; TREATMENT-OUTCOME |
| Region | National |
| NRR Data Provider | National Coordinating Centre for Health Technology Assessment (NCCHTA) |
| Funding organisation: name 1 | DH Technology Assessment Reviews Contract |
| Funding reference number 1 | 01/26/01 |
| Supplementary information | Draft final report received. |
| Contact name(s) | Dr Alison Round |
| Contact details | Public Health & Policy North & East Devon Health Authority Dean Clarke House Southernhay East Exeter, EX1 1PQ Tel: 01392 207457 Fax: 01392 207377 Email: ali.round@eastdevon-pct.nhs.uk |
| Further information | This record was taken from the National Research Register 2003, Issue 1, published in February 2003. Further information about this trial can be obtained from the lead researcher named above. |
| Date live in mRCT | 6 February 2003 |
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