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Ph 3 Trial of Blinatumomab vs Investigator's Choice of Chemotherapy in Patients With Relapsed or Refractory ALL

This study has been terminated.
(DMC recommended that the study be halted due to survival benefit of the blinatumomab arm. Amgen accepted this recommendation.)
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT02013167
First received: December 3, 2013
Last updated: April 13, 2017
Last verified: April 2017
  Purpose
This study seeks adult subjects with Relapsed/Refractory (R/R) B-precursor ALL. This is a phase 3 randomized, open label study designed to evaluate the efficacy of blinatumomab versus investigator choice of SOC chemotherapy. Adult subjects with R/R B-precursor ALL will be randomized in a 2:1 ratio to receive blinatumomab or treatment with investigator choice of 1 of 4 protocol defined SOC chemotherapy regimens. Primary Endpoint is Overall Survival.

Condition Intervention Phase
Adult Subjects With 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 ]

Other Outcome Measures:
  • Blinatumomab steady state concentration (Css) [ Time Frame: Approximately 2 years ]
  • ALLSS scores for participants [ Time Frame: Approximately 2 years ]
  • Investigation for mutations in the tumor DNA to predict resistance to blinatumomab treatment [ Time Frame: Approximately 2 years ]

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
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. In the first induction cycle, the initial dose of blinatumomab will be 9 μg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles (beginning with the second induction cycle and continuing through consolidation and maintenance, for applicable subjects) 28 μg/day will be the dose for all 4 weeks of continuous treatment.
Drug: Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. In the first induction cycle, the initial dose of blinatumomab will be 9 μg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles (beginning with the second induction cycle and continuing through consolidation and maintenance, for applicable subjects) 28 μg/day will be the dose for all 4 weeks of continuous treatment.
Active Comparator: Standard of Care Chemotherapy
Subjects randomized to receive SOC chemotherapy will be assigned to one of four chemotherapy regimens per investigator´s choice.
Drug: Standard of Care Chemotherapy
Drug: FLAG ± anthracycline based regimen (Idarubicin, fludarabine, cytarabine) Dose: Idarubicin 10mg/m2 days 1, 3: cytarabine 2g/m2 IV days 1-5; fludarabine 30 mg/m2 days 1-5 Dose: Subject's age >60: Idarubicin 5 mg/m2 day 1,3; fludarabine 20 mg/m2 days 1-5; cytarabine 1 g/m2 days 1-5 Drug: High dose cytarabine: cytarabine arabinoside ± anthracycline and/or in comb with native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents Dose: Cytarabine arabinoside at least 1 g/m2 or < per day Drug: High-dose methotrexate in combination with native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents Dose: High-dose methotrexate such as 500 mg/m2 - 3 g/m2 HDMTX (infusion time up to 24 hours) Drug: Clofarabine or clofarabine based regimens Dose: Clofarabine use as single agent: recommended prescribing info. Clofarabine combination based regimens should use ≥ 20 mg/m2/day for up to 5 days.

  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
  • or 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
    • Age ≥ 18 years at the time of informed consent
    • Subject has provided informed consent or subject's legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
  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
Study First Received: December 3, 2013
Last Updated: April 13, 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 April 28, 2017