Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers.

Abstract:

:Hematide is an investigational pegylated synthetic peptide that stimulates erythropoiesis in animal models and is being developed for the treatment of anemia associated with chronic renal failure and cancer. This study evaluated the safety and pharmacodynamics of single, intravenous doses (0.025, 0.05, and 0.1 mg/kg) of Hematide in 28 healthy male volunteers. All doses of Hematide were well tolerated, with safety profiles similar to those of placebo. Hematide showed a dose-dependent increase in reticulocytes. The 0.1-mg/kg dose was associated with a statistically significant increase in hemoglobin (Hgb) from baseline compared to the placebo group (13.6 +/- 3.9 g/L [1.36 +/- 0.39 g/dL] versus 3.9 +/- 3.8 g/L [0.39 +/- 0.38 g/dL]; P < .001) that was sustained for longer than 1 month. These results support phase 2 studies in patients with anemia associated with chronic kidney disease or cancer and suggest that Hematide administered as infrequently as once a month may result in a sustained elevation of Hgb levels. (Please note that Hematide is a proposed trade name; the compound does not yet have a nonproprietary name.).

journal_name

Blood

journal_title

Blood

authors

Stead RB,Lambert J,Wessels D,Iwashita JS,Leuther KK,Woodburn KW,Schatz PJ,Okamoto DM,Naso R,Duliege AM

doi

10.1182/blood-2006-04-015818

subject

Has Abstract

pub_date

2006-09-15 00:00:00

pages

1830-4

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2006-04-015818

journal_volume

108

pub_type

杂志文章,随机对照试验

相关文献

BLOOD文献大全
  • Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.

    abstract::Two sisters in whom a diagnosis of Fanconi's anemia was made at ages 12 and 18 subsequently developed acute nonlymphocytic leukemia (ANLL). A third sibling had previously died at age 11 of apparent sepsis. Both sisters had cytogenetic studies that showed increased chromosomal breakage and a 46,XX karyotype, but subseq...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stivrins TJ,Davis RB,Sanger W,Fritz J,Purtilo DT

    更新日期:1984-07-01 00:00:00

  • Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines.

    abstract::Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Matsuda T,Takahashi-Tezuka M,Fukada T,Okuyama Y,Fujitani Y,Tsukada S,Mano H,Hirai H,Witte ON,Hirano T

    更新日期:1995-02-01 00:00:00

  • The EMT regulator ZEB2 is a novel dependency of human and murine acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale short hairpin RNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer ty...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-05-714493

    authors: Li H,Mar BG,Zhang H,Puram RV,Vazquez F,Weir BA,Hahn WC,Ebert B,Pellman D

    更新日期:2017-01-26 00:00:00

  • Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs.

    abstract::CD99 is a crucial regulator of the transmigration (diapedesis) of leukocytes through the blood vessel wall. Here, we report that CD99 acts at 2 different steps in the extravasation process. In agreement with previous antibody-blocking experiments, we found that CD99 gene inactivation caused neutrophil accumulation bet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-08-733394

    authors: Goswami D,März S,Li YT,Artz A,Schäfer K,Seelige R,Pacheco-Blanco M,Jing D,Bixel MG,Araki M,Araki K,Yamamura KI,Vestweber D

    更新日期:2017-03-30 00:00:00

  • Control of GVHD: it's in our DNA!

    abstract::Selective depletion of the alloreactive T cells causing graft-versus-host disease (GVHD) without loss of the graft-versus-leukemia (GVL) effect is the holy grail of hematopoietic cell transplantation (HCT). In this issue of Blood, He et al demonstrate that inhibition of histone methylation leads to selective apoptosis...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2011-12-395905

    authors: Chao N

    更新日期:2012-02-02 00:00:00

  • Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia.

    abstract::The underlying pathways that lead to relapse in childhood acute lymphoblastic leukemia (ALL) are unknown. To comprehensively characterize the molecular evolution of relapsed childhood B-precursor ALL, we used human 500K single-nucleotide polymorphism arrays to identify somatic copy number alterations (CNAs) in 20 diag...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-06-165027

    authors: Yang JJ,Bhojwani D,Yang W,Cai X,Stocco G,Crews K,Wang J,Morrison D,Devidas M,Hunger SP,Willman CL,Raetz EA,Pui CH,Evans WE,Relling MV,Carroll WL

    更新日期:2008-11-15 00:00:00

  • Retinoic acid inhibits interleukin-6-induced macrophage differentiation and apoptosis in a murine hematopoietic cell line, Y6.

    abstract::We established a radiation-induced murine hematopoietic cell line, Y6, that could be induced to differentiate into macrophages by interleukin-6 (IL-6). IL-6 also induced growth inhibition and apoptosis in Y6 cells. Retinoic acid (RA) inhibited such effects of IL-6 on Y6 cells. The inhibitory effect of RA on the effect...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Oritani K,Kaisho T,Nakajima K,Hirano T

    更新日期:1992-11-01 00:00:00

  • The clinical applications of genome editing in HIV.

    abstract::HIV/AIDS has long been at the forefront of the development of gene- and cell-based therapies. Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer genome editing technologies based on engineered nucleases are now all...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-01-678144

    authors: Wang CX,Cannon PM

    更新日期:2016-05-26 00:00:00

  • Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system.

    abstract::Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rinehart J,Delamater EW,Keville L,Measel J

    更新日期:1994-09-01 00:00:00

  • Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group.

    abstract::AALL07P2 evaluated whether substitution of Erwinia asparaginase 25000 IU/m(2) for 6 doses given intramuscularly Monday/Wednesday/Friday (M/W/F) to children and young adults with acute lymphoblastic leukemia and clinical allergy to pegaspargase would provide a 48-hour nadir serum asparaginase activity (NSAA) ≥ 0.10 IU/...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2013-01-480822

    authors: Salzer WL,Asselin B,Supko JG,Devidas M,Kaiser NA,Plourde P,Winick NJ,Reaman GH,Raetz E,Carroll WL,Hunger SP

    更新日期:2013-07-25 00:00:00

  • Rabbit and rat platelets do not respond to thrombin receptor peptides that activate human platelets.

    abstract::Human platelets are aggregated and induced to release their granule contents and form thromboxane by peptides as short as 6-amino acid residues (SFLLRN) corresponding to the newly released N-terminus of the thrombin receptor that is cleaved by thrombin. Using washed platelets, we found that these responses to SFLLRN (...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kinlough-Rathbone RL,Rand ML,Packham MA

    更新日期:1993-07-01 00:00:00

  • Differential regulation of tissue factor and plasminogen activator inhibitor by human mononuclear cells.

    abstract::Fibrin is a hallmark of immune-mediated tissue lesions. The presence of fibrin in such lesions implies both the formation of fibrin via coagulation and the accompanying restriction of fibrinolysis, allowing fibrin to persist. Previous work has shown that human monocytes exposed to an inflammatory stimulus such as lipo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Schwartz BS,Bradshaw JD

    更新日期:1989-10-01 00:00:00

  • The small 11 kDa nonstructural protein of human parvovirus B19 plays a key role in inducing apoptosis during B19 virus infection of primary erythroid progenitor cells.

    abstract::Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and drastically destroys erythroid progenitor cells, thus leading to most of the disease outcomes associated with B19V infection. In this study, we systematically examined the 3 B19V nonstructural proteins, 7.5 kDa, 11 kDa, and NS1, for their funct...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-04-215756

    authors: Chen AY,Zhang EY,Guan W,Cheng F,Kleiboeker S,Yankee TM,Qiu J

    更新日期:2010-02-04 00:00:00

  • Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin.

    abstract::Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan. Fully iron-saturated lactoferrin suppressed the numbers of granulocytes and monocytes per femur, the numbers of granulocyte-macrophage progenitor cells (CF...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gentile P,Broxmeyer HE

    更新日期:1983-05-01 00:00:00

  • Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma.

    abstract::Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to stri...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019001694

    authors: Frigault MJ,Dietrich J,Martinez-Lage M,Leick M,Choi BD,DeFilipp Z,Chen YB,Abramson J,Crombie J,Armand P,Nayak L,Panzini C,Riley LS,Gallagher K,Maus MV

    更新日期:2019-09-12 00:00:00

  • Inhibition of human bone marrow fibroblast colony formation by leukemic cells.

    abstract::The number of bone marrow fibroblast colony formations decreases in most cases of acute leukemia before the initiation of chemotherapy. This study was undertaken to clarify the mechanism of suppression of fibroblast colony formation in leukemic patients. Titration of the number of bone marrow cells did not indicate a ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nagao T,Yamauchi K,Komatsuda M,Noguchi K,Shimizu M,Yonekura S,Nozaki H

    更新日期:1983-12-01 00:00:00

  • Genetic expression of adenosine deaminase in human lymphoid malignancies.

    abstract::Adenosine deaminase (ADA) is an enzyme in the purine catabolic pathway that has been used as an enzymatic marker of T cell lymphoblastic malignancies due to its high specific activity in thymocytes and immature T cells. We have investigated whether the level of ADA activity in lymphoid leukemic cells correlates with t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gan TE,Dadonna PE,Mitchell BS

    更新日期:1987-05-01 00:00:00

  • Treatment of baboon with vinblastine: insights into the mechanisms of pharmacologic stimulation of Hb F in the adult.

    abstract::Vinblastine was administered to anemic baboons to test whether stimulation of Hb F takes place following distortion of erythropoiesis by an M-stage-specific compound. The treatments elicited erythroid cell cytoreduction followed by regeneration. During the phase of reticulocyte reduction, gamma/gamma + beta biosynthet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Veith R,Papayannopoulou T,Kurachi S,Stamatoyannopoulos G

    更新日期:1985-08-01 00:00:00

  • Imprinting of insulin-like growth factor 2 is modulated during hematopoiesis.

    abstract::The transcription of insulin-like growth factor 2 (IGF-2) is affected by genomic imprinting, a multistep process through which the parental origin of a gene influences its transcription. The maternal copy of IGF-2 is silenced in most human tissues, but in the choroid plexus and the adult liver both alleles of IGF-2 ar...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Morison IM,Eccles MR,Reeve AE

    更新日期:2000-11-01 00:00:00

  • Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma.

    abstract::Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lym...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chatterjee M,Barcos M,Han T,Liu XL,Bernstein Z,Foon KA

    更新日期:1990-11-01 00:00:00

  • Purification and functional characterization of homodimeric gamma B-gamma B fibrinogen from rat plasma.

    abstract::Heterogeneity in the human and rat plasma fibrinogen (FBG) gamma chains is due to differential splicing of the primary gamma chain mRNA transcript. The subunit composition of FBG containing the predominant form of the gamma chain is homodimeric (human: A alpha 2, B beta 2, gamma 50-gamma 50; rat: A alpha 2, B beta 2, ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lawrence SO,Wright TW,Francis CW,Fay PJ,Haidaris PJ

    更新日期:1993-10-15 00:00:00

  • Characterization and use of an antibody detecting the CBFbeta-SMMHC fusion protein in inv(16)/t(16;16)-associated acute myeloid leukemias.

    abstract::The inv(16)(p13q22) and t(16;16)(p13;q22) cytogenetic abnormalities occur commonly in acute myeloid leukemia (AML), typically associated with French-American-British (FAB) AML-M4Eo subtype. Reverse transcriptase-polymerase chain reaction (RT-PCR) techniques have been recently developed to detect the presence of severa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Viswanatha DS,Chen I,Liu PP,Slovak ML,Rankin C,Head DR,Willman CL

    更新日期:1998-03-15 00:00:00

  • Genetic correction of p67phox deficient chronic granulomatous disease using peripheral blood progenitor cells as a target for retrovirus mediated gene transfer.

    abstract::Chronic granulomatous disease (CGD) can result from any of four single gene defects involving the components of the superoxide (O-2) generating phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We show that transduction of peripheral blood CD34+ hematopoietic progenitors from a p67phox deficient C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Weil WM,Linton GF,Whiting-Theobald N,Vowells SJ,Rafferty SP,Li F,Malech HL

    更新日期:1997-03-01 00:00:00

  • Two-faced T cells in CLL.

    abstract::In this issue of Blood, Bagnara et al describe the development of a reliable and convincing xenograft model of CLL that recapitulates aspects of the leukemic microenvironment and gives intriguing insights into disease biology. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2011-03-342709

    authors: Devereux S

    更新日期:2011-05-19 00:00:00

  • Regulation of early human hematopoietic (BFU-E and CFU-GEMM) progenitor cells in vitro by interleukin 1-induced fibroblast-conditioned medium.

    abstract::Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators o...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zucali JR,Broxmeyer HE,Dinarello CA,Gross MA,Weiner RS

    更新日期:1987-01-01 00:00:00

  • Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis.

    abstract::In 65 patients with hemophagocytic lymphohistiocytosis (HLH), we found an as yet undescribed heterogeneity of defects in cellular cytotoxicity when assay conditions were modified by the incubation time, the presence of mitogen, or interleukin-2 (IL-2). The standard 4-hour natural killer (NK) test against K562 targets ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2001-12-0260

    authors: Schneider EM,Lorenz I,Müller-Rosenberger M,Steinbach G,Kron M,Janka-Schaub GE

    更新日期:2002-10-15 00:00:00

  • Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia.

    abstract::Eph receptors and their ephrin ligands are involved in normal hematopoietic development and tumorigenesis. Using methylated CpG island amplification/DNA promoter microarray, we identified several EPH receptor and EPHRIN genes as potential hypermethylation targets in acute lymphoblastic leukemia (ALL). We subsequently ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-05-222208

    authors: Kuang SQ,Bai H,Fang ZH,Lopez G,Yang H,Tong W,Wang ZZ,Garcia-Manero G

    更新日期:2010-03-25 00:00:00

  • The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5 HIV-1 gp120 in human macrophages.

    abstract::CCR5 is a receptor for several beta chemokines and the entry coreceptor used by macrophage-tropic (R5) strains of HIV-1. In addition to supporting viral entry, CCR5 ligation by the HIV-1 envelope glycoprotein 120 (gp120) can activate intracellular signals in macrophages and trigger inflammatory mediator release. Using...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-12-012815

    authors: Tomkowicz B,Lee C,Ravyn V,Cheung R,Ptasznik A,Collman RG

    更新日期:2006-08-15 00:00:00

  • All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol.

    abstract::We previously reported a benefit for all-trans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is rep...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2002-02-0632

    authors: Tallman MS,Andersen JW,Schiffer CA,Appelbaum FR,Feusner JH,Woods WG,Ogden A,Weinstein H,Shepherd L,Willman C,Bloomfield CD,Rowe JM,Wiernik PH

    更新日期:2002-12-15 00:00:00

  • Double-negative (CD4- CD8-) T cells from adult T-cell leukemia patients also have poor expression of the T-cell receptor alpha beta/CD3 complex.

    abstract::We present four patients with adult T-cell leukemia (ATL) derived from a novel T-cell subset (CD4-, CD8- [double-negative, DN], T-cell receptor [TCR] alpha beta+). In the ATL cells of these patients, neither gene nor surface expression of CD4 and CD8 antigens was detected. Clinical and laboratory data showed no differ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Suzushima H,Asou N,Nishimura S,Nishikawa K,Wang JX,Okubo T,Naito M,Hattori T,Takatsuki K

    更新日期:1993-02-15 00:00:00