DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, Decitabine, and Nivolumab in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

Conditions:   Acute Myeloid Leukemia;   Blasts 30 Percent or Less of Bone Marrow Nucleated Cells;   Chronic Myelomonocytic Leukemia;   High Risk Myelodysplastic Syndrome;   Myelodysplastic Syndrome;   Refractory Anemia Interventions:   Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401;   Drug: Decitabine;   Other: Laboratory Biomarker Analysis;   Biological: Nivolumab;   Drug: Poly ICLC Sponsors:   Roswell Park Cancer Institute;   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials

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Authors: Ding WJ, Yang Y, Chen ZX, Wang YY, Dong WL, Cen JN, Qi XF, Jiang F, Chen SN Abstract Previous studies on the pathogenesis of myelodysplastic syndrome (MDS) have identified multiple associated gene mutations, including mutations of tetmethylcytosinedioxygenase 2, isocitrate dehydrogenase [NADP(+)] 1 cytosolic, isocitrate dehydrogenase [NADP(+)] 2 mitochondrial and additional sex combs like 1 transcriptional regulator, all of which may be considered epigenetic regulators. Furthermore, mutations of RAS type GTPase family genes have been identified in 10-15% patients with MDS. The authors' previous study on th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Myelodysplastic syndrome (MDS) is a heterogeneous group of disorders characterized by clonal, dysplastic, ineffective hematopoiesis and an increased propensity to develop acute myeloid leukemia (AML) [1]. Approximately 60% to 80% of patients with MDS experience symptomatic anemia, and 40% to 50% may develop transfusion-dependent anemia. Transfusion-dependent anemia is associated with the development of iron overload and decreased survival. However, iron overload may occur before patients become transfusion-dependent, since ineffective erythropoiesis suppress hepcidin production in the liver and may lead to increased iron a...
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
This study may open up new potential therapeutic avenues for the treatment of patients with chronic infection, inflammatory diseases, and cancer.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells Source Type: research
Conclusions. ISV is widely used in hematological pts with IFI also in diseases other than acute myeloid leukemia and it is overall well tolerated. ORR to ISV is at least comparable with other antifungal agents. A rec/ref underlying hematological disease impacts both on OS and response to ISV, while having an IFI refractory to other antifungal agents including azoles does not seem to compromise the response to ISV, although this promising result should be confirmed in prospective studies and larger groups of patients.DisclosuresBusca: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Sp...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Conclusion: This study sheds lights on the understanding of the cooperative effect between epigenetic alterations and signaling pathways in accelerating the progression of myeloid malignancies and provides a rationale therapeutic strategy for the treatment of myeloid malignancies with ASXL1 and RAS pathway gene mutations.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 602. Disordered Gene Expression in Hematologic Malignancy, including Disordered Epigenetic Regulation: Epigenetic Modification Source Type: research
Conclusions: Overall, lurbinectedin was safe and tolerated using the schedules and dose levels tested. While no sustained remissions were observed, single-agent lurbinectedin was transiently leukemia suppressive for some patients.DisclosuresRodríguez: PharmaMar: Employment. Ravandi: Bristol-Myers Squibb: Research Funding; Jazz: Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Orsenix: Honoraria; Seattle Genetics: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honoraria; Orsenix: Honora...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research
Conclusions: FT-2102 preclinical evaluations suggest a low risk of clinically significant CYP-mediated drug-drug interaction and QTc prolongation. SA FT-2102 is well tolerated in AML and MDS, with 150 mg BID selected as the RP2D based on safety, PK and PD (2-HG) response. Significant clinical activity has been observed in heavily pre-treated and in TN patients, both in AML and MDS. FT-2102 continues being investigated at a dose of 150 mg BID in a Phase 2 study. Three SA Phase 2 cohorts are currently open for enrollment in R/R AML, AML/MDS with CR/CRi (i.e., with MRD), and in pts with R/R MDS/AML with prior exposure to an I...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I Source Type: research
Background: MDS comprise a group of disorders characterized by bone marrow (BM) failure, cytogenetic and molecular alterations, and progression to acute myeloid leukemia (AML). Most lower-risk MDS patients (pts) eventually need chronic red blood cell (RBC) transfusions because of impaired hematopoiesis, resulting in iron overload (IO) that damages organ function and contributes to shortened survival. Though iron chelation therapy (ICT) has been consistently shown to improve outcomes in lower-risk MDS pts, most studies had limitations (eg retrospective analyses, registry studies, pts not stratified by performance status). A...
Source: Blood - Category: Hematology Authors: Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Novel Therapeutics I Source Type: research
In conclusion, a MAC regimen offers higher disease-free survival for those aged 18-54 years and can tolerate MAC regimens. For patients who are unable to tolerate MAC regimens, regardless of their age, TBI200 cGy/Cy/Flu is preferred to Flu/Mel ± TT to minimize NRM risks.DisclosuresShah: Juno Pharmaceuticals: Honoraria; Lentigen Technology: Research Funding; Exelexis: Equity Ownership; Geron: Equity Ownership; Miltenyi: Other: Travel funding, Research Funding; Oncosec: Equity Ownership. Brunstein: Gamidacell: Research Funding. Champlin: Otsuka: Research Funding; Sanofi: Research Funding. Hamadani: Celgene Corporation...
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Conditioning Intensity and Novel Approaches with Targeted therapy Source Type: research
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