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

This study has been terminated.
(Decision by Evidence Generation Team 18Feb16 to prematurely discontinue LTFU as per DMC recommendation & Amgen acceptance that study had met primary endpoint)
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT02013167
First received: December 3, 2013
Last updated: May 30, 2017
Last verified: May 2017
  Purpose
The primary objective was to evaluate the effect of blinatumomab on overall survival when compared to standard of care (SOC) chemotherapy.

Condition Intervention Phase
Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia Drug: Blinatumomab Drug: Standard of Care Chemotherapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Approximately 3-4 years ]

Secondary Outcome Measures:
  • Number of Participants with CR within 12 weeks of treatment initiation. [ Time Frame: Approximately 12 weeks ]
  • Duration of CR [ Time Frame: Approximately 2 years ]
  • Duration of CR/CRh*/CRi [ Time Frame: Approximately 2 years ]
  • Number of participants with MRD remission (defined as MRD level below 10-4 by PCR or flow cytometry) [ Time Frame: Approximately 2 years ]
  • Time to a 10 point decrease from baseline in global health status and QoL scale using EORTC QLQ-C30, or EFS event [ Time Frame: Approximately 2 years ]
  • Number of participants with AlloHSCT with or without blinatumomab treatment [ Time Frame: Approximately 2 years ]
  • Number of participants with adverse events [ Time Frame: Approximately 2 years ]
  • Number of participants reaching 100-day mortality after alloHSCT [ Time Frame: 100 days ]
  • Number of participants with anti-blinatumomab antibody formation [ Time Frame: Approximately 2 years ]
  • Number of participants with a change in select vital sign and laboratory parameters [ Time Frame: Approximately 2 years ]
  • Number of Participants with CR/CRh*/CRi within 12 weeks of treatment initiation. [ Time Frame: Approximately 12 weeks ]
  • Number of Participants with event Free Survival (EFS) [ Time Frame: Approximately 12 weeks ]

Enrollment: 405
Actual Study Start Date: January 3, 2014
Study Completion Date: March 14, 2017
Primary Completion Date: December 29, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Blincyto®
  • AMG 103
  • MT103
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02013167

  Show 117 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02013167     History of Changes
Other Study ID Numbers: 00103311
2013-000536-10 ( EudraCT Number )
Study First Received: December 3, 2013
Last Updated: May 30, 2017

Keywords provided by Amgen:
Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blinatumomab
Antineoplastic Agents
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 26, 2017