scholarly journals Five‐year survival follow‐up of a phase III randomised trial comparing ofatumumab versus physicians' choice for bulky fludarabine‐refractory chronic lymphocytic leukaemia: a short report

2020 ◽  
Vol 189 (4) ◽  
pp. 689-693
Author(s):  
Udvardy Miklos ◽  
Vladimir Strugov ◽  
Catharina Lewerin ◽  
Sebastian Grosicki ◽  
Grzegorz Mazur ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Randomised Trial ◽  
Phase Iii ◽  
Short Report

Consolidation with Alemtuzumab in First Remission Induces Pronounced MRD Reduction and Clinical Remissions - Update on a Randomized Phase III Trial of the German CLL Study Group (GCLLSG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2506-2506 ◽  
Author(s):  
Matthias Ritgen ◽  
C. Schweighofer ◽  
Günther Fingerle-Rowson ◽  
Barbara Eichhorst ◽  
Raimunde Busch ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Late Stage ◽  
Clinical Remission ◽  
Lymphocytic Leukaemia ◽  
Phase Iii ◽  
Remission Induction ◽  
Control Group ◽  
Consolidation Therapy ◽  
Phase Iii Trial

Abstract The monoclonal antibody alemtuzumab is known to be effective in combination or alone in patients with late stage chronic lymphocytic leukaemia. Flow cytometric studies on minimal residual disease (MRD) showed the high potency beyond clinical response criteria even in late stage chronic lymphocytic leukaemia (CLL). The aim of the phase III trial of the GCLLSG was to investigate the role of alemtuzumab as consolidation therapy in CLL patients in first clinical remission after fludarabin (F) or F plus cyclophosphamide (FC). Patients in partial or complete clinical remission were randomized to either arm A (alemtuzumab 3 x 30 mg i.v. for up to 12 wks) or no further treatment (arm B). From 21 eligible patients 11 (1CR, 1 nPR, 9PR) were randomized to arm A. All patients received standard infection prophylaxis with famciclovir and trimethoprim/sulfamethoxazole. Before, at 6 and 12 weeks after start of consolidation therapy and regulary during follow up blood and bone marrow samples were send for molecular MRD assessment by allele specific real time PCR. The PCR allowed MRD assessment with a sensitivity of at least 10E-4 in 11 eligible cases. Results: MRD analysis showed clear reduction of CLL content by first line treatment to a median MRD level of 2.2E-3. Short after alemtuzumab treatment all treated patients showed pronounced MRD reduction to a median MRD level of 5.0E-5. During molecular follow-up median MRD level remained below 1E-4 for one year with a tendency to increase afterwards. After a median follow-up of 31.3 months from start of initial treatment occurred one relapse in the treatment arm compared to 7 of 10 in arm B. The median progression free survival (PFS) calculated from start of consolidation therapy was significantly shorter in the control group versus the treatment group (pfs 25.2; p= 0.04). Nevertheless due to severe acute infections (CTC III and IV) this study had to be stopped prematurely. Conlusion: The addition of alemtuzumab as a consolidation regimen after remission induction by F or FC is highly effective and leads to sustained MRD reduction below 10E-4. This translates into significant improved clinical outcome even in this small patient cohort compared to the control group. Encouraged by the molecular responses the GCLLSG initiated a new phase I/II trial as a dose finding study in CLL patients after F based induction of clinical remission.

scholarly journals Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2021 ◽  
Vol 32 (1) ◽  
pp. 23-33 ◽  
Author(s):  
B. Eichhorst ◽  
T. Robak ◽  
E. Montserrat ◽  
P. Ghia ◽  
C.U. Niemann ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Chronic Lymphocytic Leukaemia ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Lymphocytic Leukaemia

Results of POUT: A phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 407-407 ◽  
Author(s):  
Alison Jane Birtle ◽  
John David Chester ◽  
Robert Jones Jones ◽  
Mark Johnson ◽  
Michaela Hill ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Randomised Trial ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Stopping Rules ◽  
Phase Iii ◽  
Early Stopping ◽  
Cross Sectional ◽  
Free Survival

407 Background: The role of post nephro-ureterectomy (NU) treatment for UTUC is unclear. POUT (CRUK/11/027; NCT01993979) addresses whether adjuvant chemotherapy improves disease free survival (DFS) for pts with histologically confirmed pT2-T4 N0-3 M0 UTUC. Methods: Pts (max n = 345) ≤90 days post NU were randomised (1:1) to 4 cycles of gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance with subsequent chemotherapy if required. Pts had 6 monthly cross sectional imaging and cystoscopy for the first 2 years, then annually to 5 years. Toxicity was assessed by CTCAE v4. Primary endpoint was DFS. The trial was powered to detect a hazard ratio (HR) of 0.65 (i.e. improvement in 3 year DFS from 40% to 55%; 2-sided alpha = 5%, 80% power) with Peto-Haybittle (p < 0.001) early stopping rules for efficacy & inefficacy. Secondary endpoints included metastasis-free survival (PFS), overall survival (OS), toxicity & quality of life. Results: Between May 2012 & Sept 2017, 248 pts were recruited (123 surveillance; 125 chemotherapy) at 57 UK centres. In Oct 2017, the independent trial oversight committees recommended POUT close to recruitment as data collected thus far (data snapshot 05/09/2017) met the early stopping rule for efficacy. At the time of interim analysis, median follow-up was 17.6 months (IQR 7.5-33.6). Pts had median age 69 years (range 36-88), 30% pT2, 65% pT3; 91% pN0;. Grade ≥3 toxicities were reported in 60% chemotherapy pts & 24% surveillance pts. 47/123 (surveillance) & 29/125 (chemotherapy) DFS events were reported; unadjusted HR = 0.47 (95% CI: 0.29, 0.74) in favour of chemotherapy (log-rank p = 0.0009). Two year DFS was 51% for surveillance (95% CI: 39, 61) and 70% for chemotherapy (95% CI: 58, 79). PFS favoured chemotherapy: HR = 0.49 (95% CI: 0.30, 0.79, p = 0.003). Conclusions: Adjuvant chemotherapy improved PFS in UTUC. POUT is the largest randomised trial in this pt population; the trial was terminated early because of efficacy favouring the chemotherapy arm. Whilst follow up for OS continues, this should be considered a new standard of care in these patients. Clinical trial information: ISRCTN98387754.

The prognostic value of smudge cells (Gumprecht shadows) in chronic lymphocytic leukaemia

2012 ◽  
Vol 153 (44) ◽  
pp. 1732-1737 ◽  
Author(s):  
László Szerafin ◽  
János Jakó ◽  
Ferenc Riskó ◽  
Zsuzsanna Hevessy
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Prognostic Value ◽  
Blood Smear ◽  
Lymphocytic Leukaemia ◽  
Annexin V ◽  
Inverse Correlation ◽  
Treated Group ◽  
Time To Treatment ◽  
Cell Percentage

Introduction: Smudge cells (Gumprecht shadows) are chronic lymphocytic leukaemic cells ruptured during peripherial blood smear preparation. It has been demonstrated to be linked to reduced expression of the cytoskeletal protein vimentin and its inverse correlation with the clinical outcome of the disease. Aims: Investigation of the percentage of smudge cells, CD38-, ZAP-70-positive cells and the time to treatment in patients with chronic lymphocytic leukaemia. Methods: Authors investigated the percentage of smudge cells, CD38- and ZAP-70-positive cells in the peripheral blood of 50 patients with chronic lymphocytic leukaemia and their correlation with the time to treatment. Results: 21 patients required treatment in the follow-up period. Their median smudge cell percentage was 9.9%, while it was 26.8% in the non-treated group. The cut-off value of smudge cell positivity was set to 20%. 59.3% of the patients with less than cut-off had to be treated in the follow-up time compared to 21.7% of patients with more smudge cells. These findings were similar to the prognostic value of CD38 and ZAP-70. The necessity of treatment increased to 75–77.8% with the combination of investigated markers. The time to treatment was 19 months when smudge cells were less than 20%, but above 20% it was 36.15 months. In case of low smudge cell percentage and CD38 positivity the time to treatment was 14.14 months and in case of high smudge cell percentage and CD38 negativity it was 32.92 months. In discordant cases the time to treatment was 18.43 months. The authors also present a case report that demonstrates the relationship between the percentage of smudge cells and apoptotic cells with annexin V and 7-AAD staining. Conclusions: Estimation of smudge cells on a blood smear could be a simple and cheap prognostic test in chronic lymphocytic leukaemia with sensitivity similar to CD38 and ZAP-70 estimation. Combination of these tests raised the sensitivity of their prognostic value. Orv. Hetil., 2012, 153, 1732–1737.

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