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- | Amsidine (amsacrine) / Kyowa Kirin
Journal: Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation. (Pubmed Central) - Apr 29, 2024
We further visualize DltB in an apo form, in complex with DltC, and in complex with its inhibitor amsacrine (m-AMSA)...The tetrameric organization of DltB provides a scaffold for catalyzing D-alanyl transfer and regulating the channel opening and closing. Our findings unveil DltB's dual function in the D-alanylation pathway, and provide insight for targeting DltB as a anti-virulence antibiotic.
- | Amsidine (amsacrine) / Kyowa Kirin, Rubraca (rucaparib) / Pharma& Schweiz
Journal, PARP Biomarker: Unraveling the Molecular Complexity of Adenoid Cystic Carcinoma (ACC): A Comprehensive Exploration of Hub Genes, Protein-Protein Interaction (PPI) Networks, microRNA (miRNA) Involvement, and Drug-Gene Interactions (DGIs). (Pubmed Central) - Mar 25, 2024
The dysregulation of microRNAs and transcription factors adds complexity to ACC's molecular profile. Exploration of drug-gene interactions reveals promising therapeutic strategies, involving FDA-approved drugs such as amsacrine and rucaparib, providing avenues for personalized interventions.
- REGPARA / Kyowa Kirin, Amsidine (amsacrine) / Kyowa Kirin
GENETIC BIOMARKERS PREDICTING PROGNOSIS IN PATIENTS WITH CHOLANGIOCARCINOMA; A BIOINFORMATICS APPROACH STUDY (Hall A, Poster Hall - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_3805;
Identification of certain genes by bioinformatic approach can optimize prognostication in patients with CC. It also shed light into mechanistic pathways and suggest potential pharmacologic targets for management of CC.
- Ovastat (treosulfan) / Medac, Medexus, Amsidine (amsacrine) / Kyowa Kirin
SEQUENTIAL CONDITIONING DOES NOT IMPROVE OUTCOMES OF ALLOGENEIC STEMCELL TRANSPLANTATION IN CMML PATIENTS (GALA) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2520;
This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu)...FLAMSA-FB regimen consists of fludarabine (30 mg/m2 ; total dose 120 mg/m2 ), amsacrine (100 mg/m2 ; total dose 400 mg/m 2 ), and cytarabine (1 g/m2 ; total dose 4 g/m 2 ) therapy from days -11 to minus -8, followed by a three-day interval without therapy and Busulfan from day -4 to -2 with a total dose of 6.4mg/Kg and Fludarabine on day -4 and -3 (30 mg/m2, total dose 60mg/m 2 ).Treo-Flu regimen consisted of Treosulfan (12 g/m2 , total dose 36 mg/m2 ) on days-6 to -4 and fludarabine (30 mg/m2 ; total dose 150 mg/m2 ) on days -6 to -2... Our study suggests that sequential conditioning with FLAMSA-FB does not improve Transplant outcomes in patients undergoing allo-SCT for CMML.
- Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Amsidine (amsacrine) / Kyowa Kirin, Rydapt (midostaurin) / Novartis
Real-World Treatment Patterns and Clinical Outcomes in Newly Diagnosed Acute Myeloid Leukemia with and without mIDH1 Treated with Intensive Chemotherapy from an International Real-World Data... (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4777;
Patients received IC in combination with targeted therapies (mainly midostaurin) in 18% of the IC population in France and 12.4% of the IC population in the USA...In the REAL-IDH study we observed that treatment patterns in m IDH1 or wild type patients were similar. More specific data is needed regarding the sequencing of treatment regimens and overall outcomes in m IDH1 AML patients.
- Amsidine (amsacrine) / Kyowa Kirin, seliciclib (CYC202) - Cyclacel, Cedars / Sinai
Targeting Loss of the Tumor Suppressor TENT5C in Multiple Myeloma (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4236;
Our results indicate a tumor suppressor role of TENT5C in MM, with antiproliferative properties and a susceptibility to spliceosome and NHEJ inhibitors. The HTP screen identified other targets that are currently undergoing validation leading to the identification of the molecular mechanisms underlying this function.
- Ovastat (treosulfan) / Medac, Medexus, Amsidine (amsacrine) / Kyowa Kirin
Sequential Conditioning Does Not Improve Outcomes of Allogeneic Stemcell Transplantation in CMML Patients (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2594;
This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu)...FLAMSA-FB regimen consists of fludarabine (30 mg/m 2 ; total dose 120 mg/m 2 ), amsacrine (100 mg/m 2 ; total dose 400 mg/m 2 ), and cytarabine (1 g/m 2 ; total dose 4 g/m 2 ) therapy from days -11 to minus -8, followed by a three-day interval without therapy and Busulfan from day -4 to -2 with a total dose of 6.4mg/Kg and Fludarabine on day -4 and -3 (30 mg/m 2 , total dose 60mg/m 2 ).Treo-Flu regimen consisted of Treosulfan (12 g/m 2 , total dose 36 mg/m 2 ) on days-6 to -4 and fludarabine (30 mg/m 2 ; total dose 150 mg/m 2 ) on days -6 to -2...Lastly, cumulative incidences of acute GVHD grade II-IV (TB 41%, FLAMSA-FB 35%, Treo-Flu 30%, p=0.75) and all-grade chronic GVHD (TB 50%, FLAMSA-FB 65%, Treo-Flu 40%, p=0.35) were similar across groups. Conclusion Our study suggests that sequential conditioning with FLAMSA-FB does not improve Transplant outcomes in patients undergoing allo-SCT for CMML.
- Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Sequential Allogeneic Stem Cell Transplantation (alloSCT) After Venetoclax (Ven)?Based Therapy for Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) or Myelodysplastic Syndrome With Excess Blasts 2 (MDS?EB2) () - Aug 31, 2023 - Abstract #SOHO2023SOHO_444;
Interventions: Prior to sequential alloSCT, patients received: triplet ACTIVE therapy (Ven, low-dose cytarabine, actinomycin D), n=12; FLAMSA (fludarabine, amsacrine, cytarabine) + Ven, n=1; FLAG- Ida (fludarabine, high-dose cytarabine, idarubicin, granulocyte- colony stimulating factor) + Ven, n=1; and decitabine + Ven, n=1. Sequential allotransplantation after Ven-based therapies resulted in short-term remissions and modest OS in this real-life, high-risk R/R AML or MDS-EB2 group.
- | Amsidine (amsacrine) / Kyowa Kirin
Journal, IO biomarker: Amsacrine downregulates BCL2L1 expression and triggers apoptosis in human chronic myeloid leukemia cells through the SIDT2/NOX4/ERK/HuR pathway. (Pubmed Central) - Aug 7, 2023
Altogether, the results of this study suggest that amsacrine triggers apoptosis in K562 cells by inhibiting BCL2L1 expression through the SIDT2/NOX4/ERK-mediated downregulation of HuR. Furthermore, a similar pathway also explains the cytotoxicity of amsacrine in CML MEG-01 and KU812 cells.
- | Amsidine (amsacrine) / Kyowa Kirin
Journal: In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease. (Pubmed Central) - Aug 2, 2023
Other compounds from the NCATS libraries such as the H1 antihistamine oxatomide (>5-log reduction), emetine, amsacrine an intercalator (NCGC0015113), MLS003116111-01, NCGC00247785-13, and MLS00699295-01 were found to effectively reduce VEEV viral replication in plaque assays...Rates of inactivation by CA074 in the presence of 6 mM CaCl, MnCl, or MgCl were measured with varying concentrations of inhibitor, Mg and Mn slightly enhanced inhibitor binding (3 to 6-fold). CA074 inhibited not only the VEEV nsP2 protease but also that of CHIKV and WEEV.
- | Venclexta (venetoclax) / Roche, AbbVie, Ovastat (treosulfan) / Medac, Medexus, Amsidine (amsacrine) / Kyowa Kirin
Enrollment open: Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML (clinicaltrials.gov) - Jul 3, 2023
P1/2, N=38, Recruiting, Sponsor: Heinrich-Heine University, Duesseldorf
CA074 inhibited not only the VEEV nsP2 protease but also that of CHIKV and WEEV. Not yet recruiting --> Recruiting
- | Venclexta (venetoclax) / Roche, AbbVie, Ovastat (treosulfan) / Medac, Medexus, Amsidine (amsacrine) / Kyowa Kirin
New P1/2 trial: Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML (clinicaltrials.gov) - Apr 11, 2023
P1/2, N=38, Not yet recruiting, Sponsor: Heinrich-Heine University, Duesseldorf
- | Amsidine (amsacrine) / Kyowa Kirin
Journal, PD(L)-1 Biomarker, IO biomarker: Discovery of acridine-based LSD1 inhibitors as immune activators targeting LSD1 in gastric cancer. (Pubmed Central) - Apr 4, 2023
Not yet recruiting --> Recruiting In this study, we screened an in-house small-molecule library targeting LSD1, an FDA-approved drug amsacrine for acute leukemia and malignant lymphomas was found to exhibit moderate anti-LSD1 inhibitory activity (IC
- Evusheld (cilgavimab/tixagevimab) / AstraZeneca, Xevudy (sotrovimab) / GSK, National Institutes of Health, Vir Biotech, National Institute of Allergy and Infectious Diseases
Neutralising efficacy of sotrovimab, but not tixagevimab/cilgavimab in vitro is retained against SARS-CoV-2 Omicron variants of concern XBB and BQ.1.1 (C / 05) - Apr 2, 2023 - Abstract #ECCMID2023ECCMID_5816;
- | Amsidine (amsacrine) / Kyowa Kirin
Preclinical, Journal: Interaction study with DNA/HSA, anti-topoisomerase II?, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds. (Pubmed Central) - Mar 24, 2023
In this study, we screened an in-house small-molecule library targeting LSD1, an FDA-approved drug amsacrine for acute leukemia and malignant lymphomas was found to exhibit moderate anti-LSD1 inhibitory activity (IC With the MCF-7 and T-47D cell lines, the lowest IC was presented by LT81 with values of 0.74?
- | Retrospective data, Journal: Amsacrine-based induction therapy in AML patients with cardiac comorbidities: a retrospective single-center analysis. (Pubmed Central) - Mar 13, 2023
TAA cannot be recommended as a substitute of standard induction for AML patients with significant concomitant cardiac disease. In the era of novel agents, alternative strategies (e.g., hypomethylating agents plus venetoclax) should be considered when anthracycline-based regimens are not suitable.
- ||| Amsidine (amsacrine) / Kyowa Kirin
We don’t have Amsacrine in the US. FLAG-IDA with allogeneic transplant in aplasia is used in the US- early relapse is very common unfortunately. (Twitter) - Feb 20, 2023
- cytarabine / Generic mfg.
TBI-BASED VERSUS CHEMOTHERAPY-BASED AMSA/ARA-C CONDITIONING REGIMENS IN PRIMARY REFRACTORY AML (ePoster Area) - Feb 11, 2023 - Abstract #EBMT2023EBMT_1058;
Of the 466 eligible patients identified, 237 (50.8%) received CT-based conditioning with busulfan-fludarabine (BuFlu) or busulfan-cyclophosphamide-fludarabine (BuCyFlu) and 229 received TBI-based conditioning with a total of 4 Gy and cyclophosphamide-fludarabine (CyFlu)... The above results highlight significantly worse outcomes in younger AML patients conditioned with AMSA/ARA-C followed by 4Gy TBI and CyFlu, likely related to TBI-associated side effects but also inability to achieve deeper responses with only 4Gy TBI.
- Venclexta (venetoclax) / Roche, AbbVie
SMART CONDITIONING WITH VENETOCLAX ENHANCED SEQUENTIAL FLAMSA+ALKYLATOR IN PATIENTS WITH HIGH-RISK MYELOID MALIGNANCIES (ePoster Area) - Feb 11, 2023 - Abstract #EBMT2023EBMT_1036;
This may be a smart way to extend the limited therapy options of patients with high-risk myeloid malignancies. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial should be the next step.
- | Amsidine (amsacrine) / Kyowa Kirin, Cognex (tacrine) / Shionogi
Journal: Acridine: A Scaffold for the development of drugs for Alzheimer's disease. (Pubmed Central) - Feb 7, 2023
Further research is required to evaluate the effectiveness of the acridine derivatives with various substitutions in the treatment of AD. In conclusion, our review will suggest the potentiality of the versatile acridine framework for drug designing and developing novel multi-target inhibitors for the Alzheimer's disease.
- || Amsidine (amsacrine) / Kyowa Kirin
Amsacrine isn't even approved in US. (Twitter) - Jan 29, 2023
- |||| Amsidine (amsacrine) / Kyowa Kirin
Clinical: Have you (or your center/transplanters) ever used FLAMSA RIC AlloBMT (4 days of Flu- amsacrine-HiDAC, then 3-day break, then RIC during aplasia with TBI 4 Gy (or Bu 8 mg/kg), Cy 80-120 mg/kg & ATG, with tapering of IST until day 90 & prophylactic DLI for patients without GvHD. (Twitter) - Jan 28, 2023
- cytarabine / Generic mfg.
Amsa/ARA-C Followed By TBI 4 Gy or High Dose Chemotherapy Conditioning Regimens in Primary Refractory AML – Significantly Worse Outcomes in Younger Patients Conditioned with 4 Gy TBI (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_6523;
This was not reflected in patients aged 55 years or more. Although only 4 Gy, these results emphasize the importance of age in the transplant physician’s decision to incorporate TBI into conditioning regimens to optimize outcomes.
- Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Sequential Use of Flamsa, FLAG, CLAG or TEC-Based Conditioning Regimen Followed By Allogeneic Hematopoietic Transplantation Results in Favorable Outcome for High Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasia Patients: 15 Year Follow-up of the Multicenter Study in Singapore (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4770;
Sequential transplant conditioning with FLAMSA, FLAG, CLAG or TEC-based cytoreductive regimen followed by allo-HCT is an effective strategy in overcoming the dismal prognosis of HR AML, MDS and MPN, including patients with high risk DRI, and enabling favorable long-term disease-free survival. More studies on effective strategies such as optimising the conditioning regimen intensity or post-transplant maintenance therapy with prophylactic donor lymphocyte infusion, are needed to further eliminate the risk of relapse, without increasing risk of treatment-related toxicity.
- | Amsidine (amsacrine) / Kyowa Kirin
Journal: Amsacrine combined with etoposide and methylprednisolone is a feasible and safe component in first-line intensified treatment of pediatric patients with high-risk acute lymphoblastic leukemia in CoALL08-09 trial. (Pubmed Central) - Nov 1, 2022
More studies on effective strategies such as optimising the conditioning regimen intensity or post-transplant maintenance therapy with prophylactic donor lymphocyte infusion, are needed to further eliminate the risk of relapse, without increasing risk of treatment-related toxicity. In conclusion, AEP is well tolerated as a component of the HR treatment and is useful in bridging-to-transplant settings.
- Ovastat (treosulfan) / Medac, Medexus, Campath (alemtuzumab) / Sanofi, Amsidine (amsacrine) / Kyowa Kirin
REDUCED INTENSITY CONDITIONING FOR ALLOGENEIC STEM CELL TRANSPLANTATION (HSCT) IN ACUTE MYELOID LEUKEMIA () - Oct 16, 2022 - Abstract #EHOC2022EHOC_35;
Efficient safe pre transplant conditioning protocols are continuing to be developed. Future protocols will most probably incorporate specific anti leukemic targeted novel compounds as well as monoclonal and radiolabeled antibodies.
- | dexamethasone / Generic mfg.
Trial completion date, Trial primary completion date: DEXAML-03: Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia (clinicaltrials.gov) - Aug 18, 2022
P3, N=142, Recruiting, Sponsor: University Hospital, Toulouse
Future protocols will most probably incorporate specific anti leukemic targeted novel compounds as well as monoclonal and radiolabeled antibodies. Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025
- | dexamethasone / Generic mfg.
Enrollment open: DEXAML-03: Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia (clinicaltrials.gov) - Aug 8, 2020
P3, N=142, Recruiting, Sponsor: University Hospital, Toulouse
Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025 Not yet recruiting --> Recruiting
- | Oncaspar liquid (pegaspargase) / Servier
Enrollment closed: Clofarabine or High-Dose Cytarabine and Pegaspargase in Children With ALL (clinicaltrials.gov) - Mar 31, 2020
P2/3, N=745, Active, not recruiting, Sponsor: Universit
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting
- | Oncaspar liquid (pegaspargase) / Servier
Trial completion date, Trial primary completion date: Clofarabine or High-Dose Cytarabine and Pegaspargase in Children With ALL (clinicaltrials.gov) - Oct 8, 2019
P2/3, N=660, Recruiting, Sponsor: Universit
Recruiting --> Active, not recruiting Trial completion date: Sep 2021 --> Dec 2024 | Trial primary completion date: Mar 2019 --> Dec 2019
- | dexamethasone / Generic mfg.
Trial completion date, Trial initiation date, Trial primary completion date: DEXAML-03: Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia (clinicaltrials.gov) - Apr 17, 2019
P3, N=142, Not yet recruiting, Sponsor: University Hospital, Toulouse
Trial completion date: Sep 2021 --> Dec 2024 | Trial primary completion date: Mar 2019 --> Dec 2019 Trial completion date: Jan 2024 --> Sep 2024 | Initiation date: Jan 2019 --> Sep 2019 | Trial primary completion date: Jan 2024 --> Sep 2024
- | Oncaspar liquid (pegaspargase) / Servier
Trial primary completion date: Clofarabine or High-Dose Cytarabine and Pegaspargase in Children With ALL (clinicaltrials.gov) - Dec 14, 2018
P2/3, N=660, Recruiting, Sponsor: Universit
Trial completion date: Jan 2024 --> Sep 2024 | Initiation date: Jan 2019 --> Sep 2019 | Trial primary completion date: Jan 2024 --> Sep 2024 Trial primary completion date: Sep 2018 --> Mar 2019
- | dexamethasone / Generic mfg.
New P3 trial: DEXAML-03: Dexamethasone in Refractory or First Relapsed Acute Myeloid Leukemia (clinicaltrials.gov) - Dec 4, 2018
P3, N=142, Not yet recruiting, Sponsor: University Hospital, Toulouse
- | Oncaspar liquid (pegaspargase) / Servier
Clinical: Clofarabine or High-Dose Cytarabine and Pegaspargase in Children With ALL (clinicaltrials.gov) - May 30, 2017
P2/3, N=660, Recruiting, Sponsor: Universitätsklinikum Hamburg-Eppendorf
Trial primary completion date: Sep 2018 --> Mar 2019 Trial primary completion date: Sep 2016 --> Sep 2018
- | Amsidine (amsacrine) / Kyowa Kirin
Trial completion: Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia (clinicaltrials.gov) - Nov 25, 2013
P3, N=2000, Completed, Sponsor: Medical Research Council
Trial primary completion date: Sep 2016 --> Sep 2018 Active, not recruiting --> Completed
- | Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
New P2 trial: A Randomised Trial of the FLAMSA-BU Conditioning Regimen in Patients with Acute Myeloid Leukaemia and Myelodysplasia Undergoing Allogeneic Stem Cell Transplantation (EUDRACT) - Sep 1, 2013
P2, N=170, Ongoing, Sponsor: University of Birmingham
- | cytarabine / Generic mfg.
Trial completion: A Randomized Phase III Study of Intensive Consolidation With High Dose Cytosine Arabinoside in Acute Myelogenous Leukemia (AML-8B) (clinicaltrials.gov) - Jul 12, 2012
P3, N=160, Completed, Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Active, not recruiting --> Completed Active, not recruiting --> Completed
- | Neupogen (filgrastim) / Kyowa Kirin, Amgen, Amsidine (amsacrine) / Kyowa Kirin
Trial completion: Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - Jun 28, 2012
P3, N=500, Completed, Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Active, not recruiting --> Completed Active, not recruiting --> Completed