Abstract:
:There is a significant need for improved therapeutics in older patients with acute leukemia. Camidanlumab tesirine is an antibody-drug conjugate against CD25, an antigen expressed in several malignancies, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This open-label, dose-escalation and -expansion study (NCT02588092) assessed the safety, activity, pharmacokinetics (PK), and immunogenicity of camidanlumab tesirine in patients with relapsed/refractory ALL/AML. A total of 35 patients (34 AML and 1 ALL) were enrolled and received camidanlumab tesirine intravenously at 3-92 μg/kg once every three weeks (Q3W, n = 26) or 30 or 37.5 μg/kg every week (QW, n = 9). One dose-limiting toxicity of maculopapular rash occurred in the 30 μg/kg QW group; the maximum tolerated dose was not reached. No additional safety concerns or adverse events (AEs) of interest were identified. The most common (>10 % of patients) Grade ≥3 treatment-emergent AEs were febrile neutropenia (25.7 %), lymphopenia, neutropenia, thrombocytopenia or fatigue (all 14.3 %), pneumonia, increased gamma-glutamyltransferase, and hypophosphatemia (each 11.4 %). No signal for serious immune-related AEs such as Guillain-Barré syndrome/polyradiculopathy was observed and there was no evidence of immunogenicity. PK showed rapid clearance with apparent half-life <2 days for conjugated and total antibody, suggesting that Q3W dosing may be insufficient for therapeutic efficacy, and prompting exploration of a QW schedule. Two patients achieved complete responses with incomplete hematologic recovery; one each at 30 and 37.5 μg/kg QW. The trial was terminated during dose escalation due to programmatic reasons other than safety. Hence, recommended dose was not determined.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Goldberg AD,Atallah E,Rizzieri D,Walter RB,Chung KY,Spira A,Stock W,Tallman MS,Cruz HG,Boni J,Havenith KEG,Chao G,Feingold JM,Wuerthner J,Solh Mdoi
10.1016/j.leukres.2020.106385subject
Has Abstractpub_date
2020-08-01 00:00:00pages
106385eissn
0145-2126issn
1873-5835pii
S0145-2126(20)30090-4journal_volume
95pub_type
杂志文章,多中心研究abstract::Glycosylation of cytokines appears to be responsible for several differences in their activity, and focusing on G-CSF, several divergences between the non-glycosylated G-CSF, Filgrastim, and the glycosylated G-CSF, Lenograstim, have been reported. To verify the role of G-CSF glycosylation in mediating these difference...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.05.027
更新日期:2011-02-01 00:00:00
abstract::Endonucleases capable of producing internucleosomal DNA cleavage are one of the key enzymes in apoptosis. We examined endonuclease activities contained in nuclei of CD34+ and erythroid cells in the bone marrow (BM) from 12 patients with the myelodysplastic syndromes. The levels of Mg(2+)-dependent and acidic endonucle...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(97)00041-6
更新日期:1997-08-01 00:00:00
abstract::The treatment of acute myeloid leukemia (AML) did not evolve profoundly in the last decades. Some improvement has been made for acute lymphoblastic leukemia (ALL). Emerging new treatment modalities, such as immunotherapy, are now beginning to be available for acute leukemia, mostly for patients suffering from ALL. Thi...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2017.06.011
更新日期:2017-09-01 00:00:00
abstract::As sensitization of leukemia cells with granulocyte colony-stimulating factor (G-CSF) can enhance the cytotoxicity of chemotherapy in myeloid malignancies, a pilot study was conducted in order to evaluate the effect of G-CSF priming combined with low-dose chemotherapy in patients with higher risk myelodysplastic syndr...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2016.07.005
更新日期:2016-09-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of t...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2017.11.013
更新日期:2018-01-01 00:00:00
abstract::Methods for ex vivo purging of neoplastic cells from harvested marrow are being developed to increase the efficacy of autologous transplantation. One approach is selective photosensitization, using sensitizing compounds and light radiation. Pyrene-containing fatty acids and lipids are potent photosensitizers, e.g. 12-...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90170-c
更新日期:1992-01-01 00:00:00
abstract::We studied differentiation inducing effects of retinoic acid (RA), 1 alpha, 25-dihydroxyvitamin D3 (D3) and interferons (IFNs), alone and in combination, on fresh myeloid leukemic cells from 8 patients. RA not only induced the differentiation of leukemic cells in 5/8 cases, but potentiated differentiation by IFNs eith...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(90)90072-h
更新日期:1990-01-01 00:00:00
abstract::We performed a systematic review and meta-analysis of all trials comparing MMF and methotrexate as GVHD prophylaxis. Our search yielded 11 studies; 3 were randomized-control trials (RCTs). While the incidence of grades 2-4 acute GVHD was comparable, the incidence of grades 3 and 4 acute GVHD was higher in patients giv...
journal_title:Leukemia research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.leukres.2013.12.012
更新日期:2014-03-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is pathognomonically elevated in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome. However, its source of overproduction is unclear. As clinical improvement is almost always associated with VEGF reduction after...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2016.09.017
更新日期:2016-11-01 00:00:00
abstract::We analyzed the function of a SEPT9-ABL1 fusion identified in a case of T-prolymphocytic leukemia with tyrosine kinase inhibitor (TKI) resistance. Five isoforms with different N-termini, including SEPT9a-ABL1, SEPT9b-ABL1, SEPT9d-ABL1, SEPT9e-ABL1 and SEPT9f-ABL1, were detected in the leukemic cells. All isoforms exce...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2014.08.015
更新日期:2014-12-01 00:00:00
abstract::Chronic B-lymphocytic leukemia (B-CLL) cells may be regulated by immune functions. In an attempt to analyze such functions, helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8) and sIL-2R and beta 2-microglobulin were measured in serum of patients at different stages of the disease. Patient...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(92)90009-v
更新日期:1992-06-01 00:00:00
abstract::The aims were to investigate the feasibility of imatinib mesylate (IM) discontinuation in chronic myeloid leukemia patients who were initially treated with IM and achieved complete molecular response (CMR). Fourteen patients were included. Ten were relapsed within 9.5 months after discontinuation of IM. All 7 patients...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2012.02.011
更新日期:2012-06-01 00:00:00
abstract::Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have recently shown a sig...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.08.018
更新日期:2010-05-01 00:00:00
abstract::Aberrant promoter methylation may contribute to the hematopoietic disturbances in myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and aberrant promoter methylation of key regulatory genes during MDS hematopoiesis. An i...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.08.014
更新日期:2009-03-01 00:00:00
abstract::Delocalized lipophilic cation dequalinium (DQA) selectively accumulates in mitochondria and displays anticancer activity in different malignancies. Our previous studies indicate a DQA-induced cytotoxicity in human acute promyelocytic leukemia NB4 cells by early disturbance in mitochondrial function and oxidative stres...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2014.01.009
更新日期:2014-07-01 00:00:00
abstract::The aim of this study was to elucidate the pathologic sequence changes and associated clinical phenotypes in 9 new patients showing homozygosity for perforin gene among a total of 37 (24%) Turkish FHL families studied by linkage analysis. These 9 unrelated patients (5M/4F) were coming from consanguineous families and ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.11.033
更新日期:2008-06-01 00:00:00
abstract::We examined polymorphisms of glutathione S-transferase (GST) genes in 159 Japanese patients with myelodysplasia and compared the incidence with that in 43 normal individuals to clarify their pathogenetic significance in myelodysplasia. In individuals with the GSTT1 null genotype, the odds ratios for disease risk were ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(99)00119-8
更新日期:1999-11-01 00:00:00
abstract::The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow (BM) failure, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia (AML). The BM microenvironment in MDS plays ...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2015.06.017
更新日期:2015-10-01 00:00:00
abstract::We describe a 79-year-old man who had massive pleural effusion and a proliferation of prolymphocytic leukemia cells in the peripheral blood, bone marrow, and pleural effusion fluid. Immunophenotyping of leukemia cells revealed either CD3+CD4+CD8-CD25+ or CD3+CD4+CD8+CD25+. The antibody against human T-cell lymphotropi...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.02.029
更新日期:2007-03-01 00:00:00
abstract::Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within 10m...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.07.009
更新日期:2009-01-01 00:00:00
abstract::A method using avidin-biotin complex (ABC) to detect the presence of the enzyme terminal deoxynucleotidyl transferase (TdT) is described and compared with a proven indirect immunofluorescence method. The material studied consisted of: (1) peripheral blood and bone marrow smears from 17 patients with leukemia (ALL, 8; ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(83)90107-8
更新日期:1983-01-01 00:00:00
abstract::A patient with myelodysplastic syndromes (MDS) developed eosinophilia during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). To study the mechanism of this eosinophilia, we investigated the proliferation of eosinophil colony-forming units (CFU-Eo) in nine patients and four...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00083-6
更新日期:1995-12-01 00:00:00
abstract::Expression of p14(ARF) and p16(INK4a) tumor suppressor genes was investigated in 109 patients with chronic myeloid leukemia (CML). The p14(ARF) and p16(INK4a) mRNA levels were significantly low in patients in chronic phase (CP) at presentation and high in patients treated with interferon-alpha (IFN-alpha), especially ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.02.002
更新日期:2006-10-01 00:00:00
abstract::Cell line PER-423 was derived from the cells of a patient with an immature acute T-lymphoblastic leukaemia and the growth of this human cell line is strictly dependent on interleukin-2 (IL-2). PER-423 cells express the p75 (beta) subunit of the IL-2 receptor (IL-2R beta), while the p55 chain (IL-2R alpha) is not detec...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90141-7
更新日期:1993-01-01 00:00:00
abstract::Delta retrovirus-mediated leukemogenesis is dependent on the oncogenic potential of Tax. It is not clear, however, whether Tax-specific immune responses play a role in leukemia onset and progression. Using the BLV-associated leukemia model in sheep, we found that Tax-specific cytotoxic responses induced by DNA immuniz...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.06.003
更新日期:2010-12-01 00:00:00
abstract::Cytogenetic analysis provides important diagnostic and prognostic information for patients with myelodysplastic syndromes (MDS). Prior studies, mostly comprised of small sample sizes, have reported conflicting results while evaluating the usefulness of FISH in addition to G-band karyotyping in MDS. In the current stud...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.09.013
更新日期:2010-04-01 00:00:00
abstract::The colony-forming capacity of the peripheral blood stem/progenitor cells (PBSC) in different forms of myelodysplastic syndrome (MDS) was investigated. In most cases of refractory anemia (RA) the colony growth of PBSC was definitely reduced as compared to the controls. However, in RA with unfavorable chromosomal aberr...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(01)00064-9
更新日期:2001-11-01 00:00:00
abstract::The polyamine transport system (PTS), hyperactive in cancer cells, can constitute a gate to deliver F14512, a novel spermine epipodophyllotoxin conjugate recently selected for clinical development in AML phase I. We investigated in vitro the high antiproliferative effect of F14512 against 13 leukemia cell lines, and d...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.12.021
更新日期:2010-10-01 00:00:00
abstract::A wide range of different agents are capable of inducing the onset of HL-60 differentiation along the myeloid lineage. The diversity of these agents has made the analysis of the molecular mechanisms involved in the regulation of the onset and progress of terminal differentiation in these cells difficult. We have adapt...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90081-7
更新日期:1989-01-01 00:00:00
abstract::One of the major limitations of DNA flow cytometry (FCM) in hematologic malignancies is the lack of information about the proliferation activity of subpopulations of the heterogeneous bone marrow (BM) compartment. We studied the S-phase DNA content of immunophenotypically defined BM subpopulations (CD2+; CD19+; CD2/CD...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(91)90467-8
更新日期:1991-01-01 00:00:00