Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment
Domenico RussoMichele MalagolaCristina SkertValeria CancelliDiamante TurriPatrizia PregnoMicaela BergamaschiM FogliNicoletta TestoniAntonio De VivoFausto CastagnettiEster PungolinoFabio StagnoMassimo BrecciaB. MartinoTamara IntermesoliGiovanna Rege CambrinGiuseppina NicoliniElisabetta AbruzzeseMario TiribelliCatia BigazziEmilio UsalaSalvatore RussoAntonella Russo‐RossiMonia LunghiMonica BocchiaAnna D’EmilioValeria SantiniMariella GirasoliRoberto Di LorenzoSimona BernardiAndrea Di PalmaBruno Mario CesanaSimona SoveriniGiovanni MartinelliGianantonio RostiMichele Baccarani
30
Citation
55
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35–59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.Keywords:
Regimen
Chronic myeloid leukaemia
Imatinib Mesylate
Interim analysis
Interim
Motivations for undertaking interim analyses differ, as do the methods proposed by different authors. This article evaluates five interim analysis procedures with regard to different requirements. The five procedures differ with respect to concern for the presence or absence of a true treatment effect. One provides interim criteria only for accepting Ho (terminating due to insufficient evidence of a true treatment effect), two provide criteria only for rejecting H(o), and the others provide criteria for either accepting or rejecting H(o). A computer program was developed to simulate applications of the interim analyses to sampling data. Actual Type I error probabilities, power, probabilities of early termination, and expected sample sizes resulting from the different interim analysis procedures are compared. One-sided and two-sided tests, equal and unequal interim sample segments, and interim alterations in the sample size or research design are considered. Results should be helpful in selecting a method that satisfies particular interests.
Interim
Interim analysis
Sample (material)
Cite
Citations (1)
This chapter discusses the important aspect of changing trial aspects, including analyzing data, before formal completion of a trial. Interim analysis (or analyses before trial is finished) should be planned and described in the study protocol, before starting the trial, to ensure the potential penalties for doing such analyses do not invalidate trial results and/or satisfy ethical requirements. The chapter discusses reasons and methods to perform interim analysis. Based on the results from interim analysis, some adjustments in the trial should be required, including early termination. Although the main goal of adaptive design is to increase the success of clinical development, making the studies more efficient and more likely to demonstrate the effect of a treatment, the investigator needs to be careful when using these methods as they can also introduce other potential biases in the study.
Interim
Interim analysis
Cite
Citations (0)
Investigators routinely perform an interim analyses to evaluate data in a clinical trial before its completion,because the trial begins with uncertainty of safety and efficacy in the proposed treatment. An interim analysis is a logical part of the trial design. This article describes how to plan and execute an interim analysis, and discusses the responsibilities of involved members.
Interim
Interim analysis
Data monitoring committee
Cite
Citations (0)
In randomized-controlled trials, interim analyses are often planned for possible early trial termination to claim superiority or futility of a new therapy. While unblinding is necessary to conduct the formal interim analysis in blinded studies, blinded data also have information about the potential treatment difference between the groups. We developed a blinded data monitoring tool that enables investigators to predict whether they observe such an unblinded interim analysis results that supports early termination of the trial. Investigators may skip some of the planned interim analyses if an early termination is unlikely. We specifically focused on blinded, randomized-controlled studies to compare binary endpoints of a new treatment with a control. Assuming one interim analysis is planned for early termination for superiority or futility, we conducted extensive simulation studies to assess the impact of the implementation of our tool on the size, power, expected number of interim analyses, and bias in the treatment effect. The numerical study showed the proposed monitoring tool does not affect size or power, but dramatically reduces the expected number of interim analyses when the effect of the treatment difference is small. The tool serves as a useful reference when interpreting the summary of the blinded data throughout the course of the trial, without losing integrity of the study. This tool could potentially save the study resources and budget by avoiding unnecessary interim analyses.
Interim
Interim analysis
Cite
Citations (2)
Interim
Interim analysis
Data monitoring committee
Cite
Citations (2)
The key ethical issues involved in developing policies for interim reports and interim analyses are considered. Then the twin topics of the appropriate contents of interim reports and the components of an appropriate interim analysis are discussed. Finally, suggested policies are offered.
Interim
Interim analysis
Cite
Citations (6)
Abstract We consider a fixed‐sample parallel‐group clinical trial with an interim analysis that tests H o : μ x = μ y against H 1 : μ x < μ y . If we do not reject at the interim analysis, then the probability of making a type I error by rejecting H o in favour of H 2 : μ x > μ y and the power at the final analysis are not appreciably affected by performing the interim analysis for certain relevant critical regions.
Interim
Interim analysis
Sample (material)
Cite
Citations (5)
Objective:To introduce the multi-armed interim analysis methods in clinical trials.Methods:Based on multi-armed analysis methods,extend the two-group group sequential interim analysis methods to multi-armed interim analysis.Results:Multi-armed interim analysis include the global test and pair-wise tests of all groups.Conclusion:The boundary for interim analysis is the key of multi-armed interim analysis.
Interim
Interim analysis
Cite
Citations (0)
In clinical trials a periodical check of safety and efficacy data is often needed. For organizational reasons it is rarely desirable to stop a trial during such an interim analysis. Therefore, new study patients are included in the trial while the interim analysis is ongoing. Disregarding the additional information provided by these interim patients would be unsatisfactory, especially for an office of regulatory affairs. Consequently, the rules for group sequential or adaptive decisions must be adjusted to the recruitment of interim patients. In this paper, two strategies for modifying study designs to consider the analysis of interim patients are proposed.
Interim
Interim analysis
Data monitoring committee
Cite
Citations (12)