scholarly journals Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias

2020 ◽  
Vol 4 (8) ◽  
pp. 1700-1710
Author(s):  
Xing Fan ◽  
Ronan Desmond ◽  
Thomas Winkler ◽  
David J. Young ◽  
Bogdan Dumitriu ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Oral Treatment ◽  
Phase 2 ◽  
Cancer Genes ◽  
Diamond Blackfan Anemia ◽  
Phase 2 Study ◽  
Prospective Phase ◽  
Low Toxicity ◽  
Thrombopoietin Mimetic ◽  
Mutation Allele

Abstract There is no standard or widely effective treatment of patients with moderate aplastic anemia (MAA) or hypo-productive uni-lineage cytopenias (UC). Eltrombopag (EPAG), a small molecule thrombopoietin mimetic, has previously been shown to result in durable multi-lineage hematologic responses with low toxicity in patients with refractory severe aplastic anemia (SAA). Its safety and efficacy in MAA are unknown. This prospective phase 2 study enrolled previously untreated and treated MAA and UC patients with clinically relevant cytopenias. EPAG was administered at doses escalating from 50 to 300 mg/d. Hematologic responses were assessed at 16 to 20 weeks. Responding patients were continued on EPAG until reaching defined robust or stable blood counts. EPAG was reinstituted for relapse. Thirty-four patients were enrolled between 2012 and 2017, including 31 with MAA and 3 with UC. Seventeen patients responded in at least 1 eligible lineage by the primary end point. A striking improvement in anemia was observed in a patient with Diamond-Blackfan anemia. EPAG was well tolerated, and it was discontinued for robust or stable blood counts in 12 of 17 patients after a median of 8 months. A majority required re-initiation of EPAG for declining counts, and all regained response. Two of 34 patients developed non–chromosome 7 bone marrow cytogenetic abnormalities while taking EPAG, without dysplasia or increased blasts. Somatic mutation allele frequencies in cancer genes did not increase overall on EPAG. EPAG is a well-tolerated oral treatment of cytopenias in patients with MAA/UC. This trial was registered at www.clinicaltrials.gov as #NCT01328587.

scholarly journals Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study

Blood ◽  
2018 ◽  
Vol 132 (7) ◽  
pp. 750-754 ◽  
Author(s):  
Regis Peffault de Latour ◽  
Sylvie Chevret ◽  
Charlotte Jubert ◽  
Anne Sirvent ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Cord Blood Transplantation ◽  
Young Patients ◽  
Phase 2 ◽  
Blood Transplantation ◽  
Phase 2 Study ◽  
Key Points ◽  
Unrelated Donors ◽  
Unrelated Cord Blood

Key Points CBT after FLU-CY-ATG-2-Gy TBI with at least 4 × 107 frozen NCs per kilogram leads to satisfactory OS in refractory SAA. CBT is a valuable curative option in young patients with refractory idiopathic SAA and no available matched unrelated donors.

scholarly journals Induction Chemotherapy Plus Simultaneous Modulated Accelerated Radiation Therapy in Non-operative Hypopharyngeal and Supraglottic Laryngeal Squamous Cell Carcinoma: Long-Term Outcome of a Prospective Phase 2 Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Boning Cai ◽  
Lingling Meng ◽  
Jingzi Mo ◽  
Shouping Xu ◽  
Baolin Qu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Long Term Outcomes ◽  
Phase 2 Study ◽  
Prospective Phase ◽  
Accelerated Radiation Therapy

Background: To evaluate the toxicities and long-term outcomes of induction chemotherapy (ICT) plus simultaneous modulated accelerated radiation therapy (SMART) in non-operative hypopharyngeal and supraglottic laryngeal squamous cell carcinoma (SCCH/L).Materials and Methods: This was a prospective phase 2 study. Patients diagnosed with SCCH/L, aged from 18 to 75, staged from III to IVB in accordance with the AJCC 2010 criteria, and refusing surgery were eligible. The patients were treated with 2–3 cycles of docetaxel-cisplatin-based ICT and SMART combined with 2–3 cycles of cisplatin-based concurrent chemotherapy. The prescription dose to the primary tumor and metastatic nodes was 69 Gy in 30 fractions. Acute and late toxicities were assessed according to the established Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and long-term outcomes were analyzed.Results: Between February 2013 and June 2015, 55 newly diagnosed SCCH/L patients were enrolled. No grade 2 or worse acute xerostomia was noted. The incidences of grade 3 acute dermatitis, oral mucositis, and pharyngoesophagitis were 12.7, 3.6, and 12.7%, respectively. The median follow-up time was 48 months (range 5.5–74 months). The main late toxicity was hoarseness or sore throat, with an incidence of 32.7%. The 5-year functional larynx-preservation survival was 51.5%. The 3- and 5-year locoregional control and overall survival were 58.2, 51.5, 63.6, and 54.1%, respectively.Conclusions: The ICT plus SMART with a regimen of 69 Gy/30 F for the treatment of SCCH/L demonstrated acceptable severe toxicity, satisfactory long-term outcomes, and laryngeal function preservation.

Liposomal cisplatin response prediction in heavily pretreated breast cancer patients: A multigene biomarker in a prospective phase 2 study.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13077-e13077 ◽  
Author(s):  
Erik Hugger Jakobsen ◽  
Dorte Nielsen ◽  
Hella Danoe ◽  
Soeren Linnet ◽  
Joergen Hansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Response Prediction ◽  
Phase 2 ◽  
Breast Cancer Patients ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Prospective Phase

Prospective phase II trial in patients with first relapse of high-grade astrocytoma using TVB-2640 in combination with bevacizumab versus bevacizumab alone.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2064-2064 ◽  
Author(s):  
Brandon Konkel ◽  
Laura D Caflisch ◽  
Adolfo Enrique Diaz Duque ◽  
Joel Michalek ◽  
Qianqian Liu ◽  
...  
Keyword(s):  
Fatty Acid Synthase ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Combined Modality Treatment ◽  
Phase 2 ◽  
High Grade Astrocytoma ◽  
Phase 2 Study ◽  
Biomarker Analysis ◽  
Prospective Phase ◽  
First Relapse

2064 Background: Recurrent glioblastoma (rGBM) following chemoradiation is associated with a poor prognosis. While bevacizumab is the most common salvage therapy, responses remain brief and without an associated survival benefit. Resistance may involve overexpression of Fatty Acid Synthase (FASN). Our institution is conducting a phase 2 study of bevacizumab with FASN inhibitor TVB-2640 in patients with GBM in first relapse. Methods: This is a prospective, phase 2 study of bevacizumab with TVB-2640 in patients with GBM in first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age ≥ 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. Randomization into two arms for the first 28 days is included for exploratory biochemical analysis: patients in arm 1 receive bevacizumab every 2 weeks in combination with TVB-2640; those in arm 2 receive bevacizumab alone every 2 weeks. MR-Spectroscopy (MRS) and serum sampling for exosome analysis are obtained on patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converge to a single arm and continue to receive bevacizumab in combination with TVB-2640. Results: We have enrolled 24 patients to date; 23 have started treatment. Of those 23 patients, 10 have died, 4 have progressed but are still alive, 2 withdrew, and 7 are still active on trial. The PFS6 is and OS9 are both currently 50%, which compares favorably with historical controls. There have been no reports of grade 4 or 5 treatment-related AEs (of note, 2 deaths were thought definitely unrelated to treatment, including 1 case of intracerebral hemorrhage, and 1 case of sepsis). There have been two cases of grade 3 hand-foot syndrome thought definitely related to treatment. Updated results will include PFS, response, and biomarker analysis (exosome, MRS). Conclusions: The combination of TVB2640 with bevacizumab appears be well tolerated. PFS6 and OS9 are both currently 50%. The study has completed accrual with final data expected later in 2019. Clinical trial information: NCT03032484.

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