Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan
A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m 2 /day for 5 da...
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| Veröffentlicht in: | International journal of hematology 2016-08, Vol.104 (2), p.245-255 |
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| creator | Koh, Katsuyoshi Ogawa, Chitose Okamoto, Yasuhiro Kudo, Kazuko Inagaki, Jiro Morimoto, Tsuyoshi Mizukami, Hideya Ecstein-Fraisse, Evelyne Kikuta, Atsushi |
| description | A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m
2
/day for 5 days, followed by 52 mg/m
2
/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m
2
/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased.
C
max
and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (
T
1/2
) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m
2
/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance. |
| doi_str_mv | 10.1007/s12185-016-2004-4 |
| format | Article |
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2
/day for 5 days, followed by 52 mg/m
2
/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m
2
/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased.
C
max
and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (
T
1/2
) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m
2
/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.</description><identifier>ISSN: 0925-5710</identifier><identifier>EISSN: 1865-3774</identifier><identifier>DOI: 10.1007/s12185-016-2004-4</identifier><identifier>PMID: 27086352</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Adenine Nucleotides - administration & dosage ; Adenine Nucleotides - adverse effects ; Adenine Nucleotides - pharmacokinetics ; Adolescent ; Arabinonucleosides - administration & dosage ; Arabinonucleosides - adverse effects ; Arabinonucleosides - pharmacokinetics ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Half-Life ; Hematology ; Humans ; Medicine ; Medicine & Public Health ; Oncology ; Original Article ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Recurrence ; Treatment Outcome</subject><ispartof>International journal of hematology, 2016-08, Vol.104 (2), p.245-255</ispartof><rights>The Japanese Society of Hematology 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-5e7aa8bb5fadd12d5193b2ab15910fb69c57ec6117a2449eaf2921db54caabe23</citedby><cites>FETCH-LOGICAL-c429t-5e7aa8bb5fadd12d5193b2ab15910fb69c57ec6117a2449eaf2921db54caabe23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12185-016-2004-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12185-016-2004-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27086352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koh, Katsuyoshi</creatorcontrib><creatorcontrib>Ogawa, Chitose</creatorcontrib><creatorcontrib>Okamoto, Yasuhiro</creatorcontrib><creatorcontrib>Kudo, Kazuko</creatorcontrib><creatorcontrib>Inagaki, Jiro</creatorcontrib><creatorcontrib>Morimoto, Tsuyoshi</creatorcontrib><creatorcontrib>Mizukami, Hideya</creatorcontrib><creatorcontrib>Ecstein-Fraisse, Evelyne</creatorcontrib><creatorcontrib>Kikuta, Atsushi</creatorcontrib><title>Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan</title><title>International journal of hematology</title><addtitle>Int J Hematol</addtitle><addtitle>Int J Hematol</addtitle><description>A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m
2
/day for 5 days, followed by 52 mg/m
2
/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m
2
/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased.
C
max
and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (
T
1/2
) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m
2
/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.</description><subject>Adenine Nucleotides - administration & dosage</subject><subject>Adenine Nucleotides - adverse effects</subject><subject>Adenine Nucleotides - pharmacokinetics</subject><subject>Adolescent</subject><subject>Arabinonucleosides - administration & dosage</subject><subject>Arabinonucleosides - adverse effects</subject><subject>Arabinonucleosides - pharmacokinetics</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Dose-Response Relationship, Drug</subject><subject>Half-Life</subject><subject>Hematology</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Recurrence</subject><subject>Treatment Outcome</subject><issn>0925-5710</issn><issn>1865-3774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkU2LFDEQhoMo7uzqD_AiAS9e2k2lk07nKIufLOhBz6GSrnay9tcmaZb59_Y4q4ggeMqhnvcpUi9jz0C8AiHMZQYJra4ENJUUQlXqAdtB2-iqNkY9ZDthpa60AXHGznO-EQKMUOYxO5NGtE2t5Y7dft5jJg48l7U78LnnYZh7TOjjRDxOfKEuYkkx8AVLpKlkfhfLnicacMnUXSbqE4YypwPHsBbiw2Fc9rMfMJctNdD6ncaIR9dHXHB6wh71OGR6ev9esK9v33y5el9df3r34er1dRWUtKXSZBBb73WPXQey02BrL9GDtiB639igDYUGwKBUyhL20krovFYB0ZOsL9jLk3dJ8-1Kubgx5kDDgBPNa3bQArTWGNP-ByoapbRojtYXf6E385qm7SM_hVALZZuNghMV0pzzdiG3pDhiOjgQ7lidO1XnturcsTqntszze_PqR-p-J351tQHyBORtNH2j9Mfqf1p_AOq7pKg</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Koh, Katsuyoshi</creator><creator>Ogawa, Chitose</creator><creator>Okamoto, Yasuhiro</creator><creator>Kudo, Kazuko</creator><creator>Inagaki, Jiro</creator><creator>Morimoto, Tsuyoshi</creator><creator>Mizukami, Hideya</creator><creator>Ecstein-Fraisse, Evelyne</creator><creator>Kikuta, Atsushi</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160801</creationdate><title>Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan</title><author>Koh, Katsuyoshi ; Ogawa, Chitose ; Okamoto, Yasuhiro ; Kudo, Kazuko ; Inagaki, Jiro ; Morimoto, Tsuyoshi ; Mizukami, Hideya ; Ecstein-Fraisse, Evelyne ; Kikuta, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-5e7aa8bb5fadd12d5193b2ab15910fb69c57ec6117a2449eaf2921db54caabe23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenine Nucleotides - administration & dosage</topic><topic>Adenine Nucleotides - adverse effects</topic><topic>Adenine Nucleotides - pharmacokinetics</topic><topic>Adolescent</topic><topic>Arabinonucleosides - administration & dosage</topic><topic>Arabinonucleosides - adverse effects</topic><topic>Arabinonucleosides - pharmacokinetics</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Dose-Response Relationship, Drug</topic><topic>Half-Life</topic><topic>Hematology</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Recurrence</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koh, Katsuyoshi</creatorcontrib><creatorcontrib>Ogawa, Chitose</creatorcontrib><creatorcontrib>Okamoto, Yasuhiro</creatorcontrib><creatorcontrib>Kudo, Kazuko</creatorcontrib><creatorcontrib>Inagaki, Jiro</creatorcontrib><creatorcontrib>Morimoto, Tsuyoshi</creatorcontrib><creatorcontrib>Mizukami, Hideya</creatorcontrib><creatorcontrib>Ecstein-Fraisse, Evelyne</creatorcontrib><creatorcontrib>Kikuta, Atsushi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koh, Katsuyoshi</au><au>Ogawa, Chitose</au><au>Okamoto, Yasuhiro</au><au>Kudo, Kazuko</au><au>Inagaki, Jiro</au><au>Morimoto, Tsuyoshi</au><au>Mizukami, Hideya</au><au>Ecstein-Fraisse, Evelyne</au><au>Kikuta, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan</atitle><jtitle>International journal of hematology</jtitle><stitle>Int J Hematol</stitle><addtitle>Int J Hematol</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>104</volume><issue>2</issue><spage>245</spage><epage>255</epage><pages>245-255</pages><issn>0925-5710</issn><eissn>1865-3774</eissn><abstract>A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m
2
/day for 5 days, followed by 52 mg/m
2
/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m
2
/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased.
C
max
and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (
T
1/2
) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m
2
/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>27086352</pmid><doi>10.1007/s12185-016-2004-4</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | International journal of hematology, 2016-08, Vol.104 (2), p.245-255 |
| issn | 0925-5710 1865-3774 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Adenine Nucleotides - administration & dosage Adenine Nucleotides - adverse effects Adenine Nucleotides - pharmacokinetics Adolescent Arabinonucleosides - administration & dosage Arabinonucleosides - adverse effects Arabinonucleosides - pharmacokinetics Child Child, Preschool Dose-Response Relationship, Drug Half-Life Hematology Humans Medicine Medicine & Public Health Oncology Original Article Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Recurrence Treatment Outcome |
| title | Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan |
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