Jaeger U.,Medical University of Vienna |
Trneny M.,Charles University |
Melzer H.,Medical University of Vienna |
Praxmarer M.,Arbeitsgemeinschaft Medikamentose Tumortherapie |
And 23 more authors.
Haematologica | Year: 2015
We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57-1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43-0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36-0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25-0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong eventfree, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials. gov as #NCT00400478. © 2015 Ferrata Storti Foundation.
Branford S.,Center for Cancer Biology |
Branford S.,University of Adelaide |
Yeung D.T.,Center for Cancer Biology |
Yeung D.T.,Australasian Leukaemia and Lymphoma Group |
And 25 more authors.
Blood | Year: 2014
In chronic myeloid leukemia (CML) patients, a breakpoint cluster region-Abelson (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with poorer outcome, yetmanyof these patients still achieve satisfactory outcomes. We in vestigated 528 first-lineimatinib-treated patients to determine whether patients with the poorestoutcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1 ≤10% at 3 months (P < .001). However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1 decline from baseline, assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1 values did not halve by 76 days(n = 21; 4-year overall survival, 95% vs 58%, P = .0002; progression-free survival, 92% vs 63%, P = .008; failure-free survival, 59% vs 6%, P < .0001; and major molecular response, 54% vs 5%, P = .008). By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study highlighted that the rate of BCR-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFNvs STI571 (IRIS) trialwas registered at http://www.clinicaltrials.gov as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www. clinicaltrials.gov as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR. org.au as #ACTRN12607000325404. © 2014 by The American Society of Hematology.
Ross D.M.,Haematology |
Ross D.M.,Flinders University |
Branford S.,Genetic Pathology |
Seymour J.F.,Australasian Leukaemia and Lymphoma Group |
And 22 more authors.
Blood | Year: 2013
Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional quantitative polymerase chain reaction (PCR) on imatinib for at least 2 years. Patients stopped imatinib and were monitored frequently for molecular relapse. At 24 months, the actuarial estimate of stable treatment-free remission was 47.1%. Most relapses occurred within 4 months of stopping imatinib, and no relapses beyond 27 months were seen. In the 21 patients treated with interferon before imatinib, a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk, as was slower achievement of UMRD after switching to imatinib. Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD, even several years after imatinib withdrawal. No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations (median follow-up, 42 months). All patients who relapsed remained sensitive to imatinib re-treatment. These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse. © 2013 by The American Society of Hematology.
Branford S.,Center for Cancer Biology |
Branford S.,University of Adelaide |
Yeung D.T.,Center for Cancer Biology |
Yeung D.T.,University of Adelaide |
And 21 more authors.
Blood | Year: 2013
Recent studies have demonstrated that some patients with chronicmyeloid leukemia (CML) can maintain remission after discontinuation of imatinib. A prerequisite is stable, undetectable BCR-ABL1. It is not known how many patients achieve this response or the factors associated with its achievement. We examined 423 de novo imatinib-treated patients to determine the cumulative incidence of achieving the discontinuation criteria as defined in the CML8 study (≥2 years of undetectable BCR-ABL1 [Stable MR4.5]), and predictive factors. After 8 years of imatinib, the cumulative incidence of Stable MR4.5 was 36.5%. Therefore, 9% to 15% of first-line imatinib-treated patients would maintain remission after discontinuation. The BCR-ABL1 level at 3 months and factors at diagnosis were examined for association with Stable MR4.5: Sokal risk, age, sex, and assigned imatinib dose. The only independent predictors were female sex (54.4% vs 27.2%; P = .018) and the 3-month BCR-ABL1 (P ≤ .001). The highest cumulative incidence of Stable MR4.5 after 8 years was 78.2% for patients with BCR-ABL1 ≤ 0.10%IS at 3 months (n = 38). Time to major molecular response (MMR) influenced the time to reach Stable MR4.5 (P < .001), suggesting slower dynamics of response with a delayed MMR. The findings justify the focus on rapid reduction of BCR-ABL1 as a strategy to maximize potential suitability for imatinib discontinuation studies. The Iris trial was registered at http://www.clinicaltrials.gov as NCT00006343. The Tops trial was registered at http://www.clinicaltrials.gov as NCT00124748. The TIDEL I trial was registered at www.ANZCTR.org.au as ACTRN12607000614493. The TIDEL II trial was registered at www.ANZCTR.org.au as ACTRN12607000325404. © 2013 by The American Society of Hematology.
Martin-Kerry J.M.,Dental Health Services Victoria |
Lamont T.J.,University of Dundee |
Keightley A.,University of Dundee |
Calache H.,Dental Health Services Victoria |
And 7 more authors.
British Dental Journal | Year: 2015
There is increasing importance placed on conducting clinical trials in dentistry to provide a robust evidence base for the treatment provided, and models of care delivered. However, providing the evidence upon which to base such decisions is not straightforward, as the conduct of these trials is complex. Currently, only limited information is available about the strategies to deliver successful clinical trials in primary care settings, and even less available on dental clinical trials. Considerable knowledge and experience is lost once a trial is completed as details about effective management of a trial are generally not reported or disseminated to trial managers and researchers. This leads to loss of vital knowledge that could assist with the effective delivery of new trials. The aim of this study is to examine the conduct and delivery of five dental clinical trials across both Australia and the UK and identify the various factors that impacted upon their implementation. Findings suggest that early stakeholder engagement, and well-designed and managed trials, lead to improved outcomes for researchers, clinic staff and patients, and increases the potential for future dissemination and translation of information into practice. © 2015 British Dental Association. All rights reserved.
PubMed | North Richmond Community Health Service, La Trobe University, Australasian Leukaemia and Lymphoma Group, Victoria University of Melbourne and 2 more.
Type: Journal Article | Journal: British dental journal | Year: 2015
There is increasing importance placed on conducting clinical trials in dentistry to provide a robust evidence base for the treatment provided, and models of care delivered. However, providing the evidence upon which to base such decisions is not straightforward, as the conduct of these trials is complex. Currently, only limited information is available about the strategies to deliver successful clinical trials in primary care settings, and even less available on dental clinical trials. Considerable knowledge and experience is lost once a trial is completed as details about effective management of a trial are generally not reported or disseminated to trial managers and researchers. This leads to loss of vital knowledge that could assist with the effective delivery of new trials. The aim of this study is to examine the conduct and delivery of five dental clinical trials across both Australia and the UK and identify the various factors that impacted upon their implementation. Findings suggest that early stakeholder engagement, and well-designed and managed trials, lead to improved outcomes for researchers, clinic staff and patients, and increases the potential for future dissemination and translation of information into practice.
Results of a phase II study of thalidomide and azacitidine in patients with clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast count acute myeloid leukemia (AML)
Kenealy M.,Cabrini Health |
Kenealy M.,Peter MacCallum Cancer Center |
Kenealy M.,University of Melbourne |
Patton N.,Royal Adelaide Hospital |
And 11 more authors.
Leukemia and Lymphoma | Year: 2016
Single agent azacitidine or immunomodulatory drugs are effective in myelodysplastic syndrome (MDS), with differing target mechanisms and toxicities. Objectives of this ALLG MDS3 study in clinically advanced MDS, AMML and low blast AML were to establish safety, response and quality of life of azacitidine and thalidomide. Patients received azacitidine (75mg/m2/d sc 7days every 28 days), and oral thalidomide up to 100mg/d for maximum 12months. Eighty patients registered; median age 68 years (range 42–82), 49% IPSS int2-high. With 36.5 months follow up, patients received median 9 cycles azacitidine, 6.1mths thalidomide. Nonhematologic toxicity grade 3+ in 85%, commonly infections. Overall response rate was 63%; 26% CR were unaffected by IPSS. Median response duration 26.3months; overall survival was 28.1months. This combination azacitidine and thalidomide in clinically advanced MDS, CMML and low-blast AML was tolerable without unexpected toxicity and encouraging responses support further investigation of combination approaches with hypomethylating agent and immunomodulatory drug. © 2016 Informa UK Limited, trading as Taylor & Francis Group
Lowenthal R.M.,University of Tasmania |
Stone J.M.,Australasian Leukaemia and Lymphoma Group
Transfusion and Apheresis Science | Year: 2013
The Australasian Leukaemia and Lymphoma Group (ALLG) can trace its origins to 1973. It now encompasses virtually all the major hospitals in Australia and New Zealand that treat leukaemias and lymphomas. Over the years the Group as a whole, and members individually, have participated in many clinical treatment trials for aggressive lymphomas. Initially trials were conceived and carried out locally, but in recent years, in addition to continuing its own studies, the Group has been a major contributor to international trials including two that have been particularly influential, known as MInT and CORAL. The MInT study confirmed the value of adding rituximab to standard chemotherapy for aggressive lymphomas; CORAL helped define optimum methods of autografting for relapse. The ALLG has contributed and continues to contribute to the improving outcome for patients with aggressive lymphomas. © 2013 Elsevier Ltd.