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  1. Article ; Online: Hematopoietic stem cell mobilization for allogeneic stem cell transplantation by motixafortide, a novel CXCR4 inhibitor.

    Crees, Zachary D / Rettig, Michael P / Bashey, Asad / Devine, Steven M / Jaglowski, Samantha / Wan, Fei / Zhou, Amy / Harding, Melinda / Vainstein-Haras, Abi / Sorani, Ella / Gliko-Kabir, Irit / Grossman, Brenda J / Westervelt, Peter / DiPersio, John F / Uy, Geoffrey L

    Blood advances

    2023  Volume 7, Issue 18, Page(s) 5210–5214

    MeSH term(s) Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Peripheral Blood Stem Cell Transplantation
    Language English
    Publishing date 2023-06-15
    Publishing country United States
    Document type Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Letter
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 7153: Show issues Location:
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  2. Article ; Online: Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.

    Crees, Zachary D / Rettig, Michael P / Jayasinghe, Reyka G / Stockerl-Goldstein, Keith / Larson, Sarah M / Arpad, Illes / Milone, Giulio A / Martino, Massimo / Stiff, Patrick / Sborov, Douglas / Pereira, Denise / Micallef, Ivana / Moreno-Jiménez, Gemma / Mikala, Gabor / Coronel, Maria Liz Paciello / Holtick, Udo / Hiemenz, John / Qazilbash, Muzaffar H / Hardy, Nancy /
    Latif, Tahir / García-Cadenas, Irene / Vainstein-Haras, Abi / Sorani, Ella / Gliko-Kabir, Irit / Goldstein, Inbal / Ickowicz, Debby / Shemesh-Darvish, Liron / Kadosh, Shaul / Gao, Feng / Schroeder, Mark A / Vij, Ravi / DiPersio, John F

    Nature medicine

    2023  Volume 29, Issue 4, Page(s) 869–879

    Abstract: Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal ... ...

    Abstract Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34
    MeSH term(s) Adult ; Humans ; Multiple Myeloma/drug therapy ; Transplantation, Autologous ; Prospective Studies ; Heterocyclic Compounds/pharmacology ; Heterocyclic Compounds/therapeutic use ; Hematopoietic Stem Cell Mobilization/methods ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cells/metabolism ; Antigens, CD34/metabolism ; Granulocyte Colony-Stimulating Factor/pharmacology ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Immunologic Factors/therapeutic use
    Chemical Substances Heterocyclic Compounds ; Antigens, CD34 ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Immunologic Factors
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Clinical Trial, Phase III ; Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-023-02273-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4212: Show issues Location:
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  3. Article ; Online: Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial.

    Bockorny, Bruno / Macarulla, Teresa / Semenisty, Valerya / Borazanci, Erkut / Feliu, Jaime / Ponz-Sarvise, Mariano / Abad, David Gutierrez / Oberstein, Paul / Alistar, Angela / Muñoz, Andres / Geva, Ravit / Guillén-Ponce, Carmen / Fernandez, Mercedes Salgado / Peled, Amnon / Chaney, Marya / Gliko-Kabir, Irit / Shemesh-Darvish, Liron / Ickowicz, Debby / Sorani, Ella /
    Kadosh, Shaul / Vainstein-Haras, Abi / Hidalgo, Manuel

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2021  Volume 27, Issue 18, Page(s) 5020–5027

    Abstract: Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study ... ...

    Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC.
    Patients and methods: Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with
    Results: A total of 43 patients were enrolled. The ORR according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The DCR was 63.2% with median duration of clinical benefit of 5.7 months. In the intention-to-treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated, with toxicity comparable with the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection was 7%, lower than expected for this chemotherapy regimen.
    Conclusions: Triple combination of motixafortide, pembrolizumab, and chemotherapy was safe and well tolerated, and showed signs of efficacy in a population with poor prognosis and aggressive disease.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/secondary ; Female ; Fluorouracil/administration & dosage ; Humans ; Irinotecan/administration & dosage ; Leucovorin/administration & dosage ; Liposomes ; Male ; Middle Aged ; Nanoparticles ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Peptides/administration & dosage
    Chemical Substances 4-fluorobenzoyl-TN-14003 ; Antibodies, Monoclonal, Humanized ; Liposomes ; Peptides ; Irinotecan (7673326042) ; pembrolizumab (DPT0O3T46P) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2021-07-12
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-21-0929
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4223: Show issues Location:
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  4. Article ; Online: BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial.

    Bockorny, Bruno / Semenisty, Valerya / Macarulla, Teresa / Borazanci, Erkut / Wolpin, Brian M / Stemmer, Salomon M / Golan, Talia / Geva, Ravit / Borad, Mitesh J / Pedersen, Katrina S / Park, Joon Oh / Ramirez, Robert A / Abad, David G / Feliu, Jaime / Muñoz, Andres / Ponz-Sarvise, Mariano / Peled, Amnon / Lustig, Tzipora M / Bohana-Kashtan, Osnat /
    Shaw, Stephen M / Sorani, Ella / Chaney, Marya / Kadosh, Shaul / Vainstein Haras, Abi / Von Hoff, Daniel D / Hidalgo, Manuel

    Nature medicine

    2020  Volume 26, Issue 6, Page(s) 878–885

    Abstract: Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is ... ...

    Abstract Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC (NCT02826486). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8
    MeSH term(s) Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Agents, Immunological ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CD8-Positive T-Lymphocytes/pathology ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/pathology ; Carcinoma, Pancreatic Ductal/secondary ; Female ; Fluorouracil/administration & dosage ; Humans ; Irinotecan/administration & dosage ; Leucovorin/administration & dosage ; Liver Neoplasms/drug therapy ; Liver Neoplasms/secondary ; Lung Neoplasms/drug therapy ; Lung Neoplasms/secondary ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/pathology ; Male ; Middle Aged ; Myeloid-Derived Suppressor Cells/pathology ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Peptides/administration & dosage ; Peritoneal Neoplasms/drug therapy ; Peritoneal Neoplasms/secondary ; Receptors, CXCR4/antagonists & inhibitors ; Retroperitoneal Neoplasms/drug therapy ; Retroperitoneal Neoplasms/secondary ; Survival Rate ; T-Lymphocytes, Regulatory/pathology ; Treatment Outcome
    Chemical Substances 4-fluorobenzoyl-TN-14003 ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological ; CXCR4 protein, human ; Peptides ; Receptors, CXCR4 ; Irinotecan (7673326042) ; pembrolizumab (DPT0O3T46P) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
    Language English
    Publishing date 2020-05-25
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-020-0880-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4212: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Zs.MG 39: Show issues

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  5. Article ; Online: BL-8040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed/refractory acute myelogenous leukemia: An open-label safety and efficacy phase 2a study.

    Borthakur, Gautam / Ofran, Yishai / Tallman, Martin S / Foran, James / Uy, Geoffrey L / DiPersio, John F / Showel, Margaret M / Shimoni, Avichai / Nagler, Arnon / Rowe, Jacob M / Altman, Jessica K / Abraham, Michal / Peled, Amnon / Shaw, Stephen / Bohana-Kashtan, Osnat / Sorani, Ella / Pereg, Yaron / Foley-Comer, Adam / Oberkovitz, Galia /
    Lustig, Tzipi M / Glicko-Kabir, Irit / Aharon, Arnon / Vainstein-Haras, Abi / Kadosh, Shaul E / Samara, Emil / Al-Rawi, Ahmed N / Pemmaraju, Naveen / Bueso-Ramos, Carlos / Cortes, Jorge E / Andreeff, Michael

    Cancer

    2020  Volume 127, Issue 8, Page(s) 1246–1259

    Abstract: Background: CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high-affinity CXCR4 antagonist BL-8040 with high- ... ...

    Abstract Background: CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high-affinity CXCR4 antagonist BL-8040 with high-dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML.
    Methods: Forty-two patients received treatment with BL-8040 monotherapy for 2 days followed by a combination of BL-8040 with HiDAC for 5 days. Six escalating BL-8040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg/kg), and 1.5 mg/kg was selected as the dose for the expansion phase (n = 23).
    Results: BL-8040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL-8040 doses ≥1.0 mg/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5-mg/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5-mg/kg phase, and 21.8 months for responding patients in the 1.5-mg/kg cohort. Two days of BL-8040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold-changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts.
    Conclusions: The current results demonstrate the efficacy of CXCR4 targeting with BL-8040 and support continued clinical development in acute myelogenous leukemia.
    MeSH term(s) Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bone Marrow Cells/drug effects ; Cytarabine/administration & dosage ; Drug Administration Schedule ; Drug Resistance, Neoplasm ; Female ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/mortality ; Male ; Middle Aged ; Peptides/administration & dosage ; Peptides/adverse effects ; Peptides/pharmacokinetics ; Receptors, CXCR4/antagonists & inhibitors ; Recurrence ; Remission Induction
    Chemical Substances 4-fluorobenzoyl-TN-14003 ; CXCR4 protein, human ; Peptides ; Receptors, CXCR4 ; Cytarabine (04079A1RDZ)
    Language English
    Publishing date 2020-12-03
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.33338
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.146: Show issues Location:
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