Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
NCT ID: NCT02013167
Last Updated: 2024-03-05
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
405 participants
INTERVENTIONAL
2014-01-03
2017-03-14
Brief Summary
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Detailed Description
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The study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. The long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (DMC) that the study be stopped for benefit.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Blinatumomab
Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh\*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.
Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh\*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.
The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.
Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIV).
Standard of Care Chemotherapy
Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh\*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.
Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh\*/CRi could continue to receive SOC therapy for an additional 12 months.
Standard of Care Chemotherapy
* FLAG (fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor) ± anthracycline-based regimen (e.g. idarubicin 10 mg/m² days 1 \& 3; fludarabine 30 mg/m² days 1-5; cytarabine arabinoside 2 g/m² days 1-5). Patients \> 60 years: Idarubicin 5 mg/m² day 1 \& 3; fludarabine 20 mg/m² day 1-5; cytarabine arabinoside 1 g/m² day 1-5
* HiDAC (high-dose cytarabine arabinoside) - based regimen ≥1 g/m²/day ± anthracycline and/or in combination with other drugs such as native Escherichia coli asparaginase, polyethylene glycol linked to asparaginase (PEG-asparaginase), vinca alkaloids, steroids, etoposide or alkylating agents
* High-dose methotrexate-based regimen (HDMTX; 500 mg/m² to 3 g/m² infused up to 24 hours) in combination with native E. coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents.
* Clofarabine as a single agent as recommended in the prescribing information or clofarabine-based regimens with 20 mg/m²/day for up to 5 days.
Interventions
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Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIV).
Standard of Care Chemotherapy
* FLAG (fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor) ± anthracycline-based regimen (e.g. idarubicin 10 mg/m² days 1 \& 3; fludarabine 30 mg/m² days 1-5; cytarabine arabinoside 2 g/m² days 1-5). Patients \> 60 years: Idarubicin 5 mg/m² day 1 \& 3; fludarabine 20 mg/m² day 1-5; cytarabine arabinoside 1 g/m² day 1-5
* HiDAC (high-dose cytarabine arabinoside) - based regimen ≥1 g/m²/day ± anthracycline and/or in combination with other drugs such as native Escherichia coli asparaginase, polyethylene glycol linked to asparaginase (PEG-asparaginase), vinca alkaloids, steroids, etoposide or alkylating agents
* High-dose methotrexate-based regimen (HDMTX; 500 mg/m² to 3 g/m² infused up to 24 hours) in combination with native E. coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents.
* Clofarabine as a single agent as recommended in the prescribing information or clofarabine-based regimens with 20 mg/m²/day for up to 5 days.
Other Intervention Names
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Eligibility Criteria
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Exclusion Criteria
* Diagnosis of Burkitt's leukemia according to World Health Organization classification, or human immunodeficiency virus (HIV), Hepatitis B or C, or other clinically significant disorder
* Current relevant central nervous system (CNS) pathology or known or suspected CNS involvement
* Isolated extramedullary disease
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement
* Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab treatment, or eligibility for allogeneic HSCT at the time of enrollment
* Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks before blinatumomab treatment
* Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19 therapy) within 4 weeks of protocol-specified therapy
* Abnormal laboratory values (alanine or aspartate transaminase \[ALT or AST\] or alkaline phosphatase \[ALP\] ≥ 5 × upper limit of normal \[ULN\]; total bilirubin or creatinine ≥ 1.5 × ULN), or calculated creatinine clearance \< 60 mL/min.
18 Years
ALL
No
Sponsors
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Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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Research Site
Duarte, California, United States
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Los Angeles, California, United States
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San Francisco, California, United States
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Atlanta, Georgia, United States
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Chicago, Illinois, United States
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Baltimore, Maryland, United States
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Boston, Massachusetts, United States
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Boston, Massachusetts, United States
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Rochester, Minnesota, United States
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St Louis, Missouri, United States
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New York, New York, United States
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Durham, North Carolina, United States
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Greenville, South Carolina, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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Milwaukee, Wisconsin, United States
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St Leonards, New South Wales, Australia
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Herston, Queensland, Australia
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Adelaide, South Australia, Australia
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Parkville, Victoria, Australia
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Prahran, Victoria, Australia
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Murdoch, Western Australia, Australia
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Salzburg, , Austria
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Vienna, , Austria
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Vienna, , Austria
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Wels, , Austria
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Antwerp, , Belgium
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Bruges, , Belgium
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Brussels, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Yvoir, , Belgium
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Plovdiv, , Bulgaria
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Sofia, , Bulgaria
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Brno, , Czechia
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Hradec Králové, , Czechia
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Prague, , Czechia
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Prague, , Czechia
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Créteil, , France
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Le Chesnay, , France
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Nantes, , France
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Paris, , France
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Pessac, , France
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Pierre-Bénite, , France
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Toulouse, , France
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Berlin, , Germany
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Cologne, , Germany
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Essen, , Germany
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Frankfurt am Main, , Germany
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Freiburg im Breisgau, , Germany
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Heidelberg, , Germany
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Kiel, , Germany
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Leipzig, , Germany
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München, , Germany
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Münster, , Germany
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Tübingen, , Germany
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Ulm, , Germany
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Würzburg, , Germany
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Athens, , Greece
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Athens, , Greece
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Ioannina, , Greece
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Pátrai, , Greece
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Thessaloniki, , Greece
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Dublin, , Ireland
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Haifa, , Israel
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Jerusalem, , Israel
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Jerusalem, , Israel
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Petah Tikva, , Israel
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Tel Aviv, , Israel
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Tel Litwinsky, , Israel
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Bari, , Italy
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Bergamo, , Italy
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Bologna, , Italy
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Florence, , Italy
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Napoli, , Italy
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Novara, , Italy
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Palermo, , Italy
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Roma, , Italy
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Roma, , Italy
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Torino, , Italy
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Venezia, , Italy
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Verona, , Italy
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Mexico City, Mexico City, Mexico
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Monterrey, Nuevo León, Mexico
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Lublin, , Poland
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Warsaw, , Poland
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Warsaw, , Poland
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Wroclaw, , Poland
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Moscow, , Russia
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Nizhny Novgorod, , Russia
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Petrozavodsk, , Russia
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Saratov, , Russia
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Busan, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Salamanca, Castille and León, Spain
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Badalona, Catalonia, Spain
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Oviedo, Principality of Asturias, Spain
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Valencia, Valencia, Spain
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Madrid, , Spain
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Changhua, , Taiwan
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Taichung, , Taiwan
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Tainan City, , Taiwan
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Taipei, , Taiwan
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Adana, , Turkey (Türkiye)
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Ankara, , Turkey (Türkiye)
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Istanbul, , Turkey (Türkiye)
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Izmir, , Turkey (Türkiye)
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Bristol, , United Kingdom
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London, , United Kingdom
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Oxford, , United Kingdom
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Sheffield, , United Kingdom
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Southampton, , United Kingdom
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Sutton, , United Kingdom
Countries
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References
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Delea TE, Amdahl J, Boyko D, Hagiwara M, Zimmerman ZF, Franklin JL, Cong Z, Hechmati G, Stein A. Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective. J Med Econ. 2017 Sep;20(9):911-922. doi: 10.1080/13696998.2017.1344127. Epub 2017 Jul 11.
Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.
Dombret H, Topp MS, Schuh AC, Wei AH, Durrant S, Bacon CL, Tran Q, Zimmerman Z, Kantarjian H. Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2019 Sep;60(9):2214-2222. doi: 10.1080/10428194.2019.1576872. Epub 2019 Apr 5.
Kuchimanchi M, Zhu M, Clements JD, Doshi S. Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Br J Clin Pharmacol. 2019 Apr;85(4):807-817. doi: 10.1111/bcp.13864. Epub 2019 Feb 18.
Stein AS, Larson RA, Schuh AC, Stevenson W, Lech-Maranda E, Tran Q, Zimmerman Z, Kormany W, Topp MS. Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. Blood Adv. 2018 Jul 10;2(13):1522-1531. doi: 10.1182/bloodadvances.2018019034.
Topp MS, Zimmerman Z, Cannell P, Dombret H, Maertens J, Stein A, Franklin J, Tran Q, Cong Z, Schuh AC. Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Blood. 2018 Jun 28;131(26):2906-2914. doi: 10.1182/blood-2017-09-804658. Epub 2018 May 8.
Kantarjian HM, Zugmaier G, Bruggemann M, Wood BL, Horst HA, Zeng Y, Martinelli G. Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel). 2021 Nov 9;13(22):5607. doi: 10.3390/cancers13225607.
Horst HA, Zugmaier G, Martinelli G, Mergen N, Velasco K, Zaman F, Kantarjian H. CD19-negative relapse in adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia following treatment with blinatumomab-a post hoc analysis. Am J Hematol. 2023 Aug;98(8):E222-E225. doi: 10.1002/ajh.26988. Epub 2023 Jun 22. No abstract available.
Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
Jabbour E, Patel K, Jain N, Duose D, Luthra R, Short NJ, Zugmaier G, San Lucas A, Velasco K, Tran Q, Zaman F, Konopleva M, Kantarjian H. Impact of Philadelphia chromosome-like alterations on efficacy and safety of blinatumomab in adults with relapsed/refractory acute lymphoblastic leukemia: A post hoc analysis from the phase 3 TOWER study. Am J Hematol. 2021 Oct 1;96(10):E379-E383. doi: 10.1002/ajh.26281. Epub 2021 Jul 7. No abstract available.
Wei AH, Ribera JM, Larson RA, Ritchie D, Ghobadi A, Chen Y, Anderson A, Dos Santos CE, Franklin J, Kantarjian H. Biomarkers associated with blinatumomab outcomes in acute lymphoblastic leukemia. Leukemia. 2021 Aug;35(8):2220-2231. doi: 10.1038/s41375-020-01089-x. Epub 2021 Feb 4.
Rambaldi A, Huguet F, Zak P, Cannell P, Tran Q, Franklin J, Topp MS. Blinatumomab consolidation and maintenance therapy in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia. Blood Adv. 2020 Apr 14;4(7):1518-1525. doi: 10.1182/bloodadvances.2019000874.
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2013-000536-10
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
00103311
Identifier Type: -
Identifier Source: org_study_id
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