scholarly journals Aripiprazole in youth with intellectual disabilities: A retrospective chart study

2020 ◽  
pp. 174462952090517
Author(s):  
Eva Enneke Reurts ◽  
Pieter W Troost ◽  
Mariken Dinnissen ◽  
Sam Reijnen ◽  
Pieter J Hoekstra ◽  
...  
Keyword(s):  
Young Adults ◽  
Adverse Events ◽  
Intellectual Disabilities ◽  
Overall Response Rate ◽  
Response Rate ◽  
Open Label ◽  
Serious Adverse Events ◽  
Children And Young Adults ◽  
Clinical Global Impression Improvement

A retrospective chart study of patients on open-label aripiprazole treatment was conducted in the Netherlands to add to the knowledge of aripiprazole in children and young adults with mild and borderline intellectual disabilities (IDs). Fifty-three youths, mean age 14.7 ± 3.4 years and mean IQ 64.5 ±13.8, were included. Treatment responders were defined as “much improved” or “very much improved” based on the Clinical Global Impression -Improvement scale. For 83% of the patients, disruptive behavior was the main target symptom. The overall response rate was 30% after 1–4 weeks and 69% after 5–8 weeks. The 5–8 weeks responders showed a response rate of 64% at 22–26 weeks. Mild adverse events were observed in 53% of the patients of which fatigue and weight gain were the most common. Seven patients (13.2%) discontinued because of adverse events. In 53 children and young adults with mild and borderline IDs, aripiprazole was effective in both the short and the long term. No serious adverse events were observed.

Combined treatment with reboxetine in depressed patients with no response to venlafaxine: a 6-week follow-up study

2007 ◽  
Vol 19 (5) ◽  
pp. 291-296 ◽  
Author(s):  
Cecilio Álamo ◽  
Francisco López-Muñoz ◽  
Gabriel Rubio ◽  
Pilar García-García ◽  
Antonio Pardo
Keyword(s):  
Adverse Events ◽  
Rating Scale ◽  
Combined Treatment ◽  
Open Label ◽  
Serious Adverse Events ◽  
Multicentric Study ◽  
Intent To Treat ◽  
Events Data ◽  
Clinical Global Impression Improvement

Objective:The purpose of present study was to evaluate the efficacy of the addition of reboxetine in patients that had not previously responded, or had done so only partially, over 6 weeks of conventional pharmacological treatment with venlafaxine.Methods:This open-label, prospective and multicentric study included 40 outpatients diagnosed with major depressive disorder according to the DSM-IV criteria. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method.Results:Mean HAMD reduction was 34.9% (P < 0.0001). The percentages of responders (≥50% reduction in HAMD) and patients considered as benefiting from complete remission (HAMD ≤ 10 points) at week 6 were 27.5 and 12.5%, respectively. By the end of the treatment, the score of CGI-I decreased 24.8% (P < 0.0001). Percentage of patient improving (CGI < 4 points) was 47.5%. The most common non-serious adverse events were constipation, nervousness, anxiety and insomnia.Conclusion:These findings suggest that the combined treatment of reboxetine and venlafaxine, in venlafaxine-resistant patients, may be an effective and well-tolerated strategy.

Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7578-7578 ◽  
Author(s):  
A. Santoro ◽  
J. Voglova ◽  
N. Gabrail ◽  
T. Ciuleanu ◽  
M. Liberati ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
International Workshop ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Time To Progression ◽  
Open Label ◽  
Ecog Performance Status ◽  
Serious Adverse Events

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]

BIOV-111 a European Phase II Trial of Clofarabine (Evoltra®) in Refractory and Relapsed Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1859-1859 ◽  
Author(s):  
Pamela Kearns ◽  
Gerard Michel ◽  
Brigitte Nelken ◽  
Simon Joel ◽  
Essam Al-Ghazaly ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Cardiac Failure ◽  
Response Rate ◽  
Treated Patient ◽  
Lymphoblastic Leukemia ◽  
Safety Data ◽  
Open Label ◽  
Serious Adverse Events ◽  
Platelet Recovery

Abstract BIOV-111 is a European phase II non-randomised, open-label study of a next generation purine nucleoside analogue, clofarabine (Evoltra®), in pediatric patients with relapsed/refractory ALL. We report on the efficacy and safety data. Eligible patients (pts) had either primary refractory (2 pts) or relapsed/refractory (51 pts with ≥ 2 prior lines of treatment) ALL. Clofarabine 52mg/m2 daily × 5 days was given every 28–42 days (1 course). The primary endpoint is overall response rate (ORR) defined as either a complete response (CR) or CR without platelet recovery (CRp) after 2 courses. Adverse events (AEs) were graded according to NCI CTC (v3). Plasma, urine and intracellular clofarabine pharmacokinetics were also investigated. To date, 96 courses have been administered to 53 pts from 25 centres. The median number of prior treatments was 2 (range 1–5) and 20 pts (38%) had been previously transplanted. 8/29 pts receiving ≥2 courses responded (1CR, 7CRp) giving an ORR of 28%. Responses were observed in 14/53 (26%) pts receiving at least one course of clofarabine (6CR, 7CRp, 1 PR ). Eight (57%) responders had a prior transplant and 1 of these patients was transplanted post clofarabine. One pt with a prior transplant remains in remission at 20+ months. Four pts (1CR, 3CRp) have proceeded to transplantation. Serious adverse events (n=103) included febrile neutropenia (51/103), seizures (4/103), streptococcal septicaemia (3/103), palmo-plantar erythrodysaesthesia (2/103) and bone pain (2/103). Three hepatic events occurred (raised bilirubin, raised ALT/AST), 1 renal failure and 1 cardiac failure. AEs occurred in 4 pts. The renal and cardiac failure AE occurred in a pt with known anthracycline cardiac myopathy and renal impairment at study entry. Median end of infusion plasma clofarabine concentration (n=25) on days 1 and 2 were 1.5 (0.5–3.2) uM vs 2.0 (0.1–5.1) uM respectively (p=0.01) and were not different in pts achieving a response. Urinary clofarabine recovery on days 1, 5 and 6 (drug -free) was 48±18 %, 46±12 % and 5±3 %. Clofarabine TP analyses are ongoing. Response rates in this ongoing BIOV-111 study are consistent with the pivotal clofarabine study (CLO-212) in relapsed/refractory pediatric ALL. Notably, BIOV-111 has a lower incidence of AEs, including hepatic and renal AEs; (4% and 1% respectively vs 10% and 8% in CLO-212), possibly attributable to fewer prior treatments compared to CLO-212 (median 2 vs 3 respectively). Clofarabine achieves a significant response rate in this heavily pre-treated patient population and durable responses have been observed which may confer a survival advantage with longer follow-up.

AOP2014, a Novel Peg-Proline-Interferon Alpha-2b with Improved Pharmacokinetic Properties, Is Safe and Well Tolerated and Shows Promising Efficacy in Patients with Polycythemia Vera (PV)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 175-175 ◽  
Author(s):  
Heinz Gisslinger ◽  
Robert Kralovics ◽  
Bettina Gisslinger ◽  
Daniel Lechner ◽  
Veronika Buxhofer-Ausch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Iii ◽  
Molecular Response ◽  
Overall Response ◽  
Long Term Treatment

Abstract Abstract 175 AOP2014 is a next generation long-acting pegylated IFNa-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. AOP2014 has a distinct pharmacokinetic and pharmacodynamic profile which may potentially allow reduced dosing frequencies compared to other pegylated IFNs. This is being expected to result in improved tolerability, better compliance, and, finally, favorable long-term treatment outcomes. AOP2014 is a designated Orphan Drug in EU for treatment of patients with PV. The maximum tolerated dose (MTD), long term safety and efficacy of AOP2014, administered subcutaneously every 14 days, are the main objectives of the study. Patients with confirmed PV diagnosis, age equal or older 18 years, both naïve and cytoreduction pre-treated are eligible. After establishing the MTD, an extended cohort of 25 additional patients was planned to be recruited. European LeukemiaNet criteria were used for response assessment. 34 patients, treated by March 31, 2012 were included into this analysis: 25 in Phase I (dose-finding) and 9 in the Phase II (cohort extension). Median time from diagnosis was 24 months (range 0–180). 12 patients (35%) were HU pre-treated (mean past duration of HU pre-treatment 39 months, mean daily HU dose 950 mg). Median number of phlebotomies in the past 3 months prior to inclusion was 1 (range 0–8), a total of 21 patients (62%) were regularly phlebotomized at least once in three months prior to study entry. 11 patients (32%) had a history of thrombotic complications. Median Hct at baseline was 42% (range 36–51). Median WBC and platelet counts were 10.6*109/l (range 3.9–20.4) and 452*109/l (range 141–1019), respectively. 17 patients (50%) had splenomegaly at baseline. The median reported treatment duration was 41 weeks (range: 1 day – 80 weeks), 11 patients completed 1 year on treatment. Doses from 50 to 540 ug every two weeks were tested, 540 ug has been concluded as MTD as the highest tested dose, since no DLTs occurred in the study. The mean administered dose (both Phase I and II patients) was 287 ug. After 28 weeks of treatment (21 evaluable patients), 71% of patients had hematological response (7 CR, 33%; 8 PR, 38%), at week 36 (19 evaluable patients) 8 patients (42%) achieved a CR and 8 patients (42%) a PR, overall response rate (ORR, CR+PR) was 84%. At week 52 (1 year; 11 evaluable patients), 5 patients (46%) had CR and 5 (46%) PR, ORR was 91%; 8 (73%) patients presented with completely normalized blood values, all evaluable patients were phlebotomy free at this timepoint. 4 patients (of 12 evaluable for this measurement, 33%) had still enlarged spleen at week 52. At week 76, 2 evaluable patients were complete responders. At week 52, 1 patient (of 9 evaluable, 11%) developed partial molecular response, at week 68 3 patients (of 7 evaluable, 43%) had partial molecular response. One patient with allelic burden of 22% at baseline developed complete molecular response at week 36 (still ongoing). Mainly grade 1 and 2 adverse events were reported. A total of 358 adverse events occurred. 27 patients (79%) suffered from drug-related adverse events. 9 patients (26%) developed serious adverse events; 4 SAEs were considered to be treatment related. 5 patients (15%) discontinued their study participation prematurely, 3 of them due to adverse events (deterioration of underlying disease and two cases of depression). Acceptable tolerability and durable clinical benefits have been demonstrated in PV patients measured as overall response rate of above 90% with CRs of 46% at one year after treatment start. Phlebotomy independence and normalization of hematological parameters could be seen in most of the patients. The study continues to recruit and collect long term follow up information. Presented data support further development of AOP2014 in PV, a Phase III study is planned to start early 2013. Disclosures: Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding; Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Lechner:AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Tarmann:AOP Orphan Pharmaceuticals AG: Employment. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Zahriychuk:AOP Orphan Pharmaceuticals AG: Employment. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding.

scholarly journals Apatinib, a novel VEGFR-2 tyrosine kinase inhibitor, for relapsed and refractory nasopharyngeal carcinoma: data from an open-label, single-arm, exploratory study

2020 ◽  
Vol 38 (6) ◽  
pp. 1847-1853
Author(s):  
Ling Li ◽  
Fei Kong ◽  
Lei Zhang ◽  
Xin Li ◽  
Xiaorui Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Adverse Events ◽  
Overall Response Rate ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Open Label ◽  
Free Survival

Summary Purpose Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, has shown promising efficacy against several solid cancers, but evidence of its efficacy against relapsed and refractory nasopharyngeal carcinoma is limited. We investigated the efficacy and safety of apatinib for relapsed and refractory nasopharyngeal carcinoma in an open-label, single-arm, phase II clinical trial. Fifty-one patients with relapsed and refractory nasopharyngeal carcinoma in the First Affiliated Hospital, Zhengzhou University, who met the inclusion criteria were enrolled in the study. All patients received apatinib at an initial dose of 500 mg daily (1 cycle = 28 days). The primary and secondary endpoints were overall response rate, progression-free survival, and overall survival. We evaluated treatment effects and recorded apatinib-related adverse events by performing regular follow-ups and workup. The overall response rate (complete and partial responses) was 31.37% (16/51). The median overall survival and progression-free survival were 16 (95% CI, 9.32–22.68) and 9 months (95% CI, 5.24–12.76), respectively. Most patients tolerated treatment-related adverse events of grades 1 and 2; hypertension (29, 56.86%), proteinuria (25, 49.02%), and hand–foot syndrome (27, 52.94%) were the most common adverse events. There were no treatment-related deaths. Apatinib showed good efficacy and safety in patients with relapsed and refractory NPC.

Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis

2006 ◽  
Vol 12 (5) ◽  
pp. 639-645 ◽  
Author(s):  
D T Wade ◽  
P M Makela ◽  
H House ◽  
C Bateman ◽  
P Robson
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Controlled Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Oral Pain ◽  
Acute Study ◽  
Based Medicine ◽  
Lost To Follow Up

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21- 814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five ‘serious adverse events’ between them - two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of - tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.

scholarly journals Clofarabine with Topotecan, Vinorelbine, and Thiotepa (TVTC) in Children and Young Adults with Relapsed or Refractory Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 79-79
Author(s):  
Kavitha Ramaswamy ◽  
Christopher Forlenza ◽  
Rachel Kobos ◽  
Peter G. Steinherz ◽  
Neerav Shukla
Keyword(s):  
Bone Marrow ◽  
Young Adults ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Overall Response Rate ◽  
Response Rate ◽  
Hematopoietic Stem ◽  
Induction Regimen ◽  
Children And Young Adults ◽  
Refractory Aml

Abstract Background: Relapsed or refractory pediatric acute myeloid leukemia (AML) is an unfortunate reality in approximately 40% of children and young adults diagnosed with AML. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. Non-anthracycline based salvage regimens are crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a Clofarabine-based regimen with Topotecan, Vinorelbine, and Thiotepa (TVTC) in a cohort of patients with AML. Herein, we report on an expanded cohort of AML patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) since 2007. We report our center's experience using a Clofarabine-based regimen with Topotecan, Vinorelbine, and Thiotepa (TVTC), its overall response rate defined as complete remission (CR) and its use as a bridge to hematopoietic stem cell transplant (HSCT). Patients and Methods: All patients <25 years of age with relapsed/refractory AML, defined as >10% bone marrow involvement, who were treated with the phase 2 recommended schedule of TVTC were included in this analysis. Patients received the TVTC regimen with Topotecan 1 mg/m2/day (120 hour continuous infusion, Days 0-4), Vinorelbine 20 mg/m2/dose (Days 0, 7, 14), Thiotepa 15 mg/m2/dose (Day 2), and Clofarabine 40 mg/m2/day (Days 3-7). The regimen could be administered without hospitalization in patients who did not require hospitalization for other reasons. Most patients received antimicrobial prophylaxis starting on Day 8 with Levofloxacin and fungal prophylaxis with either Posaconazole or Voriconazole. GCSF 5mcg/kg/day was initiated on Day 8. Bone marrow evaluation was performed at the point of hematologic recovery to assess response. Overall response rate (ORR) was defined as complete remission (CR) plus complete remission without platelet recovery (CRp). Results: A total of 29 patients with relapsed (n=19) or refractory (n=10) AML were treated since 2007. Eight patients (28%) had prior hematopoietic stem cell transplantation (HSCT). The ORR of the entire cohort was 59% (17/29). The ORR of patients with relapsed vs. refractory disease was 74% (14/19) and 30% (3/10), respectively. Seventeen of 29 patients (59%) received TVTC as a 1st re-induction regimen with 59% (10/17) of those patients achieving a CR/CRp. The remaining 12 patients had TVTC as 2nd or greater regimen with 58% (7/12) of those patients achieving a CR/CRp. Among the 17 total responders in the cohort, 13 (76%) proceeded to HSCT. Of those who proceeded to HSCT, 8 of 13 are alive today (62%). Median time since HSCT is 66 months (range 14 to 107 months). The most common adverse effects were febrile neutropenia in 20 out of 29 patients (69%) which was Grade 3 or less, 3 of 29 patients (10%) with Grade 4 or greater febrile neutropenia requiring ICU admission. One patient developed an abdominal mucormycosis infection. One patient developed bone marrow aplasia and died due to sepsis 45 days after receiving TVTC. Conclusions: TVTC is an active regimen for children and young adults with relapsed/refractory AML, with an acceptable toxicity profile . Non-anthracycline containing salvage regimens are especially important as patients usually receive >400mg/m2 daunorubicin equivalents during frontline therapy. The majority of responders were successfully bridged to HSCT without exposure to additional anthracycline, with approximately half of these patients demonstrating long-term survival. TVTC warrants further exploration as a re-induction regimen in a larger cohort of patients with relapsed/refractory AML. Disclosures Kobos: Janssen Research & Development: Employment.

scholarly journals Interim results of a prospective, randomized, open-label, Phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the GLADIATOR study)

Cephalalgia ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 1343-1357 ◽  
Author(s):  
Jan Lewis Brandes ◽  
Suzanne Klise ◽  
John H Krege ◽  
Michael Case ◽  
Rashna Khanna ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acute Treatment ◽  
Electronic Diary ◽  
Open Label ◽  
Phase 3 ◽  
Post Dose ◽  
Serious Adverse Events ◽  
Long Term Study ◽  
Open Label Phase

Objectives To address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year. Methods In this prospective, randomized, open-label, Phase 3 study, patients who had completed either of two single-attack studies were offered the opportunity to be randomized 1:1 to lasmiditan 100 mg or 200 mg. Patients were asked to use lasmiditan as the first treatment for each new migraine attack of at least moderate severity. Assessments occurred at baseline and at prespecified time increments up to 48 hours after each dose of study drug using an electronic diary, and safety was assessed throughout the study. Migraine Disability Assessment (MIDAS) was assessed at each visit. Results As of the cut-off date for this interim analysis (6 March 2018), 1978 patients had received ≥ 1 lasmiditan dose and treated 19,058 migraine attacks. Overall, treatment-emergent adverse events (TEAEs) were similar to those in the single-attack studies and included dizziness (18.6%), somnolence (8.5%), and paresthesia (6.8%). The frequency of TEAEs generally decreased with subsequent attacks. No treatment-related serious adverse events and no cardiovascular TEAEs potentially due to vasoconstriction were observed. For both lasmiditan doses, efficacy measures were generally consistent over study quarters and treated attacks. Overall, across all treated attacks at 2 hours post-dose, pain freedom was observed in 26.9% of the attacks treated with lasmiditan 100 mg and 32.4% of the attacks treated with lasmiditan 200 mg. MIDAS total scores decreased over time. Conclusions The interim results of this long-term study showed intermittent lasmiditan (100 mg and 200 mg) to be generally well tolerated and efficacious for the acute treatment of migraine over a 1-year period. Trial registration number: NCT02565186; https://clinicaltrials.gov/ct2/show/NCT02565186

scholarly journals Efficacy of Lenalidomide plus Low-Dose Dexamethasone in Thai Patients with Relapsed and/or Refractory Multiple Myeloma

2021 ◽  
Vol 73 (5) ◽  
Author(s):  
Chutima Kunacheewa ◽  
Noppadol Siritanaratkul
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Median Number ◽  
Serious Adverse Events ◽  
Refractory Multiple Myeloma ◽  
Overall Response ◽  
Depth Of Response

Objective: Lenalidomide is an immunomodulatory agent with proven efficacy in the treatment of multiple myeloma. In large global clinical studies, lenalidomide plus dexamethasone has demonstrated significant improvements in the overall response rate and overall survival in patients with relapsed and/or refractory multiple myeloma, compared with a placebo and dexamethasone. This is the first study to report lenalidomide plus low-dose dexamethasone administered in Thai patients. Methods: The aim of this phase II, single-center, single-arm study was to evaluate the efficacy and safety of lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma. The primary endpoint was the overall response rate at the fourth treatment cycle. Secondary endpoints included depth of response, time to response, and adverse events. Results: In total, 15 patients with a median age of 61 years old (range 23–74 years old) who had received at least one prior anti-myeloma therapy were enrolled in the study and administered 4-week cycles of lenalidomide 25 mg/day (days 1–21) and dexamethasone 40 mg/week. Patients continued in the study until the occurrence of disease progression or serious adverse events. The overall response rate was 86% and 73.3% at the fourth and from all treatment cycles, respectively (median number of treatment cycles, 10.25), and the median dose for patients aged >60 years old was 15 mg/day. The overall response rate at the fourth cycle in patients who had received prior novel agents (bortezomib and/or thalidomide) was 81.82% compared with 100% in those who had received prior conventional therapy (p = 0.15). The most common adverse events reported were anemia and neutropenia, which were both manageable. Conclusion: Lenalidomide and low-dose dexamethasone was highly effective in Thai patients with relapsed and/or refractory multiple myeloma, with a manageable adverse event profile. These findings suggest that lenalidomide 15 mg/day is a safe and effective dose for Thai patients aged ≥60 years old.

scholarly journals Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma

2018 ◽  
Vol 36 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Milind Javle ◽  
Maeve Lowery ◽  
Rachna T. Shroff ◽  
Karl Heinz Weiss ◽  
Christoph Springfeld ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Clinical Activity ◽  
Open Label ◽  
Overall Response

Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.

Sign in / Sign up

Export Citation Format

Share Document