Randomized use of anti-GD2 antibody dinutuximab beta (DB) long-term infusion with and without subcutaneous interleukin-2 (scIL-2) in high-risk neuroblastoma patients with relapsed and refractory disease: Results from the SIOPEN LTI-trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Holger N. Lode ◽  
Dominique Valteau-Couanet ◽  
Juliet Gray ◽  
Roberto Luksch ◽  
Aleksandra Wieczorek ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Interleukin 2 ◽  
Hematological Toxicity ◽  
Antibody Concentration ◽  
Mycn Amplification ◽  
Open Label ◽  
Significant Difference ◽  
Enzyme Elevation

10014 Background: We determined the role of scIL-2 combined with long term infusion (LTI) of DB in patients (pts) with high-risk relapsed/refractory neuroblastoma. Methods: 160 pts were enrolled into an open label SIOPEN Phase II clinical trial (EudraCT 2009-018077-31). Pts were randomly assigned to receive up to 5 cycles of 100 mg/m2 DB-LTI (d8-17) and 160 mg/m2 oral isotretinoin (d19-32) (81 pts) with and without 6x106IU/m2 scIL-2 (d1-5; 8-12) (79 pts). Endpoints were toxicity, response rates and 2yrs-event free and -overall survival. Results: Between 07/2014 and 07/2017, 160 pts from 11 countries were randomised. Median follow-up is 2.6 years. Pts were well balanced between arms according to stage, age, MYCN amplification, patients with relapse and remission status. The 2yrs-EFS and -OS for DB (81 pts) vs. DB combined with scIL-2 (79 pts) was 59%±6% vs 65%±6% (p = 0.721) and 79%±5% vs 84%±4% (p = 0.904). In 97 pts with evaluable disease, a response rate of 49% (9% CR, 40% PR) vs 52% (26% CR, 26% PR) after treatment with DB vs DB and scIL-2 was observed. Grade 3&4 fever (16% vs 46%, P = 0.000), allergic reaction (1% vs 14%, P = 0.004), hematological toxicity (46% vs 66%, P = 0.013) and neurotoxicity (0% vs 8%, p = 0.003) were significantly worse in the combination arm, but no difference was seen for capillary leak, gastrointestinal, liver enzyme elevation and pain. Paraplegia possibly related to the treatment was observed in 2 pts in the combination arm, none in the arm without scIL-2, and one resolved to baseline. A subgroup of 34 pts who had a relapse and measurable disease at treatment start, showed a 2yrs-EFS and -OS in DB (17 pts) vs DB combined with scIL-2 (17 pts) of 35%±12% vs 69%±12% (p = 0.116) and 59%±12% vs 81%±10% (p = 0.167). However, this trend was statistically not significant. Pharmacokinetic and HACA response between both arms was not different with overlapping antibody concentration-time curves and a HACA response of 15/81 (19%) (DB) vs 16/79 (20%) (DB and scIL-2). Conclusions: No significant difference in efficacy of DB combined with scIL-2 and increased toxicity in this arm suggests that this schedule of scIL-2 is of no additional benefit. Clinical trial information: 2009-018077-31.

scholarly journals Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Majid Alfadhel ◽  
Marwan Nashabat ◽  
Mohammed Saleh ◽  
Mohammed Elamin ◽  
Ahmed Alfares ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Treatment ◽  
Propionic Acidemia ◽  
Methylmalonic Acidemia ◽  
First Episode ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Significant Difference ◽  
Secondary Outcomes

Abstract Background Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias. Methods The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay. Results Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels. Conclusion Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.

Phase II clinical trial with long-term infusion of anti-GD2 antibody ch14.18/CHO in combination with interleukin-2 (IL2) in patients with high risk neuroblastoma.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 10562-10562 ◽  
Author(s):  
Holger N. Lode ◽  
Dominique Valteau-Couanet ◽  
Sascha Troschke-Meurer ◽  
Carla Manzitti ◽  
Juliet Gray ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Phase Ii ◽  
Interleukin 2 ◽  
Phase Ii Clinical Trial

scholarly journals Long-term safety of nebulized formoterol: Results of a twelve-month open-label clinical trial

2008 ◽  
Vol 2 (4) ◽  
pp. 199-208 ◽  
Author(s):  
James F. Donohue ◽  
Nicola A. Hanania ◽  
Charles Fogarty ◽  
Sammy C. Campbell ◽  
Mike Rinehart ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Open Label

scholarly journals Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy

2019 ◽  
Vol 17 (12) ◽  
pp. 1497-1504
Author(s):  
Lucas K. Vitzthum ◽  
Chris Straka ◽  
Reith R. Sarkar ◽  
Rana McKay ◽  
J. Michael Randall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Short Term ◽  
Combined Androgen Blockade ◽  
Significant Difference ◽  
Androgen Blockade

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer–specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. Results: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85–1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93–1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57–0.95) and OS (SHR, 0.82; 95% CI, 0.73–0.93). Conclusions: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

Abstract 16567: Long-Term Vascular Function in CTO Recanalization. A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Juan Jose Rodriguez Arias ◽  
Josep Gomez-Lara ◽  
Juan Caballero-Borrego ◽  
Luis Ortega-Paz ◽  
Luis Teruel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vascular Function ◽  
Drug Loading ◽  
Controlled Clinical Trial ◽  
Loading Dose ◽  
Clinical Value ◽  
Open Label ◽  
Total Occlusion

Background: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT) with ticagrelor vs. clopidogrel. Methods: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. Results: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively). A higher CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p=0.027), was maintained at follow-up (AUC 34815.22±24206.06 vs. AUC 22712.47±13768.95; p=0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p=0.933), clopidogrel loading dose-related CBF increased at follow-up (p=0.039). Conclusion: The TIGER trial showed that DAPT with ticagrelor may maintain a higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with slight increase at follow-up. The clinical value of such sustained higher coronary flow should be evaluated in a larger group of patients.

scholarly journals Clinical trial of carotid artery stenting using dual-layer CASPER stent for carotid endarterectomy in patients at high and normal risk in the Japanese population

2020 ◽  
pp. neurintsurg-2020-016250
Author(s):  
Hirotoshi Imamura ◽  
Nobuyuki Sakai ◽  
Yasushi Matsumoto ◽  
Hiroshi Yamagami ◽  
Tomoaki Terada ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Carotid Artery ◽  
Carotid Endarterectomy ◽  
Carotid Artery Stenting ◽  
Peak Systolic Velocity ◽  
Cerebrovascular Event ◽  
Performance Goal ◽  
Significant Difference ◽  
Event Rates

BackgroundThe dual-layer nitinol CASPER stent was designed to prevent plaque prolapse into its strut and periprocedural stroke.ObjectiveTo conduct a clinical trial for government approval of the device in patients at either high or normal risk for carotid endarterectomy (CEA).MethodsEligible patients had ≥50% symptomatic stenosis or ≥80% asymptomatic stenosis according to the North American Symptomatic Carotid Endarterectomy Trial methods (peak systolic velocity 130 and 230 cm/s on ultrasonography, respectively). The primary endpoint was the lack of major adverse events (MAEs), defined as death, stroke, and myocardial infarction within 30 days, and ipsilateral stroke within 1 year. The performance goal was set at 90.5%. MAE rates were also compared between the CEA high- and normal-risk groups.Results140 carotid artery stenting procedures, including 40% of patients at high risk and 60% at normal risk for CEA, were performed in 13 institutes. MAEs occurred in two cases (one intraprocedural and one postprocedural stroke), and the MAE rate was 1.4%. The non-MAE rate was 98.6% according to Kaplan-Meier analysis, which was superior to the previously set performance goal. The deployment success, target lesion revascularization (TLR), in-stent restenosis, and cerebrovascular event rates were 99.3%, 2.4%, 8.5%, and 7.2%, respectively. The MAE rate in patients with normal CEA risk was 1.2%, which was similar to the high-risk CEA group, with no significant difference due to the small number of MAEs.ConclusionsThe MAE rate following use of the CASPER stent was low (1.4%). The MAE, deployment success, TLR, in-stenosis, and cerebrovascular event rates were similar to those of previous reports.

An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma

2014 ◽  
Vol 71 (5) ◽  
pp. 904-911.e1 ◽  
Author(s):  
Mina Sarah Ally ◽  
Sumaira Aasi ◽  
Ashley Wysong ◽  
Claudia Teng ◽  
Eric Anderson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Open Label
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