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

NCT02013167 | Terminated Phase 3 Results DMC

• 2 other identifiers: 001033112013-000536-10
• Study Type: interventional
• Target: 405
• Locations: 20 countries
• Sites: 111

Brief Summary

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

Conditions

Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Keywords

Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants With Complete Remission Within 12 Weeks of Treatment Initiation

  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

  12 weeks

• Event Free Survival (EFS)

  6 months

• Duration of Complete Remission

  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)

  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.

Study Arms (2)

Blinatumomab

EXPERIMENTAL

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

Standard of Care Chemotherapy

ACTIVE COMPARATOR

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

Interventions

Blinatumomab DRUG

Blinatumomab is administered as a continuous intravenous infusion (CIV).

Also known as: Blincyto®, AMG 103, MT103

Blinatumomab

Standard of Care Chemotherapy DRUG

* 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.

Standard of Care Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (117)

Research Site

Duarte, California, 91010, United States

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Los Angeles, California, 90095, United States

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San Francisco, California, 94143, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21201, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02215, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10065, United States

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Durham, North Carolina, 27710, United States

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Greenville, South Carolina, 29607, United States

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Nashville, Tennessee, 37232, United States

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Houston, Texas, 77030, United States

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Milwaukee, Wisconsin, 53226, United States

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St Leonards, New South Wales, 2065, Australia

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Herston, Queensland, 4029, Australia

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Adelaide, South Australia, 5000, Australia

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Parkville, Victoria, 3050, Australia

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Prahran, Victoria, 3181, Australia

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Murdoch, Western Australia, 6150, Australia

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Salzburg, 5020, Austria

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Vienna, 1090, Austria

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Vienna, 1140, Austria

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Wels, 4600, Austria

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Antwerp, 2060, Belgium

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Bruges, 8000, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Yvoir, 5530, Belgium

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Plovdiv, 4000, Bulgaria

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Sofia, 1756, Bulgaria

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Brno, 625 00, Czechia

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Hradec Králové, 500 05, Czechia

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Prague, 100 34, Czechia

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Prague, 128 20, Czechia

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Créteil, 94010, France

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Le Chesnay, 78157, France

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Nantes, 44093, France

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Paris, 75475, France

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Pessac, 33604, France

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Pierre-Bénite, 69495, France

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Toulouse, 31059, France

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Berlin, 12200, Germany

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Cologne, 50937, Germany

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Essen, 45147, Germany

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Frankfurt am Main, 60590, Germany

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Freiburg im Breisgau, 79106, Germany

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Heidelberg, 69120, Germany

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Kiel, 24116, Germany

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Leipzig, 04103, Germany

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München, 81377, Germany

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Münster, 48149, Germany

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Tübingen, 72076, Germany

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Ulm, 89081, Germany

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Würzburg, 97080, Germany

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Athens, 10676, Greece

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Athens, 11527, Greece

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Ioannina, 45110, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 57010, Greece

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Dublin, 8, Ireland

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Haifa, 31096, Israel

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Jerusalem, 91031, Israel

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Jerusalem, 91120, Israel

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Petah Tikva, 49100, Israel

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Tel Aviv, 64239, Israel

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Tel Litwinsky, 52621, Israel

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Bari, 70124, Italy

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Bergamo, 24127, Italy

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Napoli, 80131, Italy

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Novara, 28100, Italy

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Palermo, 90146, Italy

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Roma, 00133, Italy

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Roma, 00161, Italy

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Torino, 10126, Italy

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Venezia, 30174, Italy

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Verona, 37134, Italy

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Mexico City, Mexico City, 07760, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Lublin, 20-081, Poland

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Warsaw, 02-776, Poland

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Warsaw, 04-141, Poland

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Wroclaw, 50-367, Poland

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Moscow, 125167, Russia

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Nizhny Novgorod, 603126, Russia

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Petrozavodsk, 185019, Russia

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Saratov, 410012, Russia

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Busan, 614-735, South Korea

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Seoul, 110-744, South Korea

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Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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Salamanca, Castille and León, 37007, Spain

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Badalona, Catalonia, 08916, Spain

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Oviedo, Principality of Asturias, 33011, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28041, Spain

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Changhua, 50006, Taiwan

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Taichung, 40447, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 10002, Taiwan

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Adana, 01330, Turkey (Türkiye)

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Ankara, 06100, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Bristol, BS2 8ED, United Kingdom

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London, NW3 2PF, United Kingdom

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Oxford, OX3 7LJ, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Related Publications (12)

• 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.

  PMID: 28631497 BACKGROUND

• 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.

  PMID: 28249141 BACKGROUND

• 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.

  PMID: 30947585 BACKGROUND

• 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.

  PMID: 30645768 BACKGROUND

• 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.

  PMID: 29954814 BACKGROUND

• 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.

  PMID: 29739753 BACKGROUND

• 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.

  PMID: 34830762 BACKGROUND

• 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.

  PMID: 37345570 BACKGROUND

• 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.

  PMID: 35622074 DERIVED

• 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.

  PMID: 34161631 DERIVED

• 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.

  PMID: 33542479 DERIVED

• 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.

  PMID: 32289160 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: December 17, 2013
• Study Start: January 3, 2014
• Primary Completion: December 29, 2015
• Study Completion: March 14, 2017
• Last Updated: March 5, 2024
• Results First Posted: August 9, 2017

Record last verified: 2024-03

Locations

RU (4); BU (2); CZ (4); PL (4); TU (4); AU (4); CA (2); DE (13); US (16); ME (2); GR (5); IL (6); KR (4); BE (6); ES (5); IE (1); IT (12); GB (6); TW (4); FR (7)