Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

A Phase 3, Randomized, Open Label Study Investigating the Efficacy of the BiTE Antibody Blinatumomab Versus Standard of Care Chemotherapy in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (TOWER Study)

The primary objective was to evaluate the effect of blinatumomab on overall survival when compared to standard of care (SOC) chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab; Drug: Standard of Care Chemotherapy

Detailed Description

Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens. Randomization was stratified by age (< 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent.

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.

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Research Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Research Site
    • Prahran, Victoria, Australia, 3181
      • Research Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Research Site
• Austria
  • Salzburg, Austria, 5020
    • Research Site
  • Wels, Austria, 4600
    • Research Site
  • Wien, Austria, 1090
    • Research Site
  • Wien, Austria, 1140
    • Research Site
• Belgium
  • Antwerpen, Belgium, 2060
    • Research Site
  • Brugge, Belgium, 8000
    • Research Site
  • Bruxelles, Belgium, 1200
    • Research Site
  • Ghent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Sofia, Bulgaria, 1756
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 2, Czechia, 128 20
    • Research Site
• France
  • Creteil Cedex, France, 94010
    • Research Site
  • Le Chesnay, France, 78157
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
  • Paris Cedex 10, France, 75475
    • Research Site
  • Pessac Cedex, France, 33604
    • Research Site
  • Pierre-Benite, France, 69495
    • Research Site
  • Toulouse cedex 9, France, 31059
    • Research Site
• Germany
  • Berlin, Germany, 12200
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Frankfurt am Main, Germany, 60590
    • Research Site
  • Freiburg, Germany, 79106
    • Research Site
  • Heidelberg, Germany, 69120
    • Research Site
  • Kiel, Germany, 24116
    • Research Site
  • Köln, Germany, 50937
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • München, Germany, 81377
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 10676
    • Research Site
  • Ioannina, Greece, 45110
    • Research Site
  • Patra, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 57010
    • Research Site
• Ireland
  • Dublin, Ireland, 8
    • Research Site
• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
  • Tel Aviv, Israel, 64239
    • Research Site
  • Tel Hashomer, Israel, 52621
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Bergamo, Italy, 24127
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Firenze, Italy, 50134
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Novara, Italy, 28100
    • Research Site
  • Palermo, Italy, 90146
    • Research Site
  • Roma, Italy, 00161
    • Research Site
  • Roma, Italy, 00133
    • Research Site
  • Torino, Italy, 10126
    • Research Site
  • Venezia, Italy, 30174
    • Research Site
  • Verona, Italy, 37134
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
  • Seoul, Korea, Republic of, 138-736
    • Research Site
  • Seoul, Korea, Republic of, 110-744
    • Research Site
• Mexico
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 07760
      • Research Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Research Site
• Poland
  • Lublin, Poland, 20-081
    • Research Site
  • Warszawa, Poland, 04-141
    • Research Site
  • Warszawa, Poland, 02-776
    • Research Site
  • Wroclaw, Poland, 50-367
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 125167
    • Research Site
  • Nizhny Novgorod, Russian Federation, 603126
    • Research Site
  • Petrozavodsk, Russian Federation, 185019
    • Research Site
  • Saratov, Russian Federation, 410012
    • Research Site
• Spain
  • Madrid, Spain, 28041
    • Research Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Research Site
  • Castilla León
    • Salamanca, Castilla León, Spain, 37007
      • Research Site
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Research Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Research Site
• Taiwan
  • ChangHua, Taiwan, 50006
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
• Turkey
  • Adana, Turkey, 01330
    • Research Site
  • Ankara, Turkey, 06100
    • Research Site
  • Istanbul, Turkey, 34093
    • Research Site
  • Izmir, Turkey, 35340
    • Research Site
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Research Site
  • London, United Kingdom, NW3 2PF
    • Research Site
  • Oxford, United Kingdom, OX3 7LJ
    • Research Site
  • Sheffield, United Kingdom, S10 2JF
    • Research Site
  • Southampton, United Kingdom, SO16 6YD
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • San Francisco, California, United States, 94143
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• Subjects with Philadelphia negative B-precursor ALL, with any of the following:

  • refractory to primary induction therapy or refractory to salvage therapy,
  • in untreated first relapse with first remission duration <12 months
  • in untreated second or greater relapse
  • relapse at any time after allogeneic HSCT
• Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy.
• Greater than 5% blasts in the bone marrow
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria

• Malignancy other than ALL within 5 years before blinatumomab treatment, except for adequately treated selected cancers without evidence of disease
• 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
• Known exclusion criteria to investigator choice of SOC chemotherapy (per package insert)
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Blinatumomab; Blinatumomab is administered as a continuous intravenous infusion (CIV).; Other Names: AMG 103; MT103; Blincyto®
Active Comparator: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive.	From randomization until the data cut-off date of 04 January 2016; median observation time was 11.8 months in the SOC group and 11.7 months in the blinatumomab group.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Remission Within 12 Weeks of Treatment Initiation	Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete Remission (CR) was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1,000/μl. CR must have occurred within 12 weeks of the first dose of therapy.	12 weeks
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) Within 12 Weeks of Treatment Initiation	Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts. Complete remission was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and ANC > 1,000/μl. Complete Remission with partial hematological recovery (CRh*) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl. Complete remission with incomplete hematological recovery (CRi) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000 (but not both).	12 weeks
Event Free Survival (EFS)	Event free survival was defined as the time from randomization until a documented relapse after achieving CR/CRh*/CRi or death, whichever occurred first. Participants who failed to achieve a CR/CRh*/CRi within 12 weeks of treatment initiation were considered as non-responders and assigned an EFS duration of 1 day. Participants still alive and relapse-free were censored on their last disease assessment date. A relapse event was any one of the following: Hematological relapse: proportion of blasts in bone marrow >5% or blasts in peripheral blood after documented CR or CRh* or CRi; Progressive disease: An increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells; Extramedullary relapse: extramedullary lesion that is new or increased by 50% from nadir as assessed by Cheson criteria. The Kaplan-Meier estimate of EFS at 6 months is reported.	6 months
Duration of Complete Remission	Duration of complete remission, calculated only for participants who achieved a CR, was calculated from the date a CR was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.	Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.0 months in the blinatumomab group.
Duration of Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi)	Duration of CR/CRh*/CRi, calculated only for participants who achieved a CR/CRh*/CRi, was calculated from the date a CR/CRh*/CRi was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.	Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.2 months in the blinatumomab group.
Percentage of Participants With Minimal Residual Disease (MRD) Within 12 Weeks of Treatment Initiation	Bone marrow samples were evaluated for MRD remission by a central laboratory. MRD remission was defined as the occurrence of an MRD level below 10^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.	12 weeks
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)		Up to the data cut-off date of 04 January 2016; maximum time on study was 23 months.
Number of Participants With Adverse Events	Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?	From first dose of protocol-specified therapy until 30 days after the last dose, up to the data cut-off date of 04 January 2016; median duration of treatment was 5 days in the SOC group and 70 days in the blinatumomab group.
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant	The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who achieved a best response of CR/CRh*CTi within 12 weeks of treatment initiation, who received an allogeneic HSCT and did not receive any additional anticancer treatment before the transplant. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.	100 days, from the date of allogeneic HSCT until the data cut-off date of 04 January 2016
Number of Participants With Anti-blinatumomab Antibodies	Anti-blinatumomab binding antibodies were evaluated using a validated electrochemiluminescence (ECL)-based assay (binding assay). Samples positive for binding were analyzed using a cell-based bioassay to determine if the detected antibodies had neutralizing properties (neutralizing assay).	Samples were collected on day 29 at the end of cycle 2 and 30 days after the last dose of blinatumomab (median duration of treatment was 70 days).
Time to a 10-point Decrease From Baseline in Global Health Status and Quality of Life or Death	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item questionnaire that assesses the health related quality of life of cancer patients. The EORTC QLQ-C30 consists of a global health status/quality of life (QoL) scale, 5 functional scales, 3 symptom scales, and 6 single items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life durig the past week on a scale from 1 (very poor) to 7 (excellent). The scale score was derived as the sum of each score and transformed to a scale from 0 to 100 where higher scores represent a high QoL. Time to a ≥10-point decrease from baseline GHS/QoL or death, whichever came first, was calculated from baseline. Participants still alive and without a 10-point decrease in GHS/QoL EORTC QLQ-C30 were censored on their last EORTC QLQ-C30 assessment date.	From randomization until the data cut-off date of 04 January 2016; EORTC QLQ-C30 was assessed on day 1, 8, 15, and 29 during cycle 1; days 1, 15, and 29 in cycle 2 and each consolidation cycle, and 30-days following the last dose of drug treatment.

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2014
• Primary Completion (Actual): December 29, 2015
• Study Completion (Actual): March 14, 2017

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (Estimated): December 17, 2013

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: 00103311; 2013-000536-10 (EudraCT Number)