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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT02013167
First received: December 3, 2013
Last updated: July 30, 2014
Last verified: July 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with CR within 12 weeks of treatment initiation. [ Time Frame: Approximately 12 weeks ] [ Designated as safety issue: No ]
  • Duration of CR [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Duration of CR/CRh*/CRi [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Number of participants with MRD remission (defined as MRD level below 10-4 by PCR or flow cytometry) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of participants with AlloHSCT with or without blinatumomab treatment [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: Approximately 2 years ] [ Designated as safety issue: Yes ]
  • Number of participants reaching 100-day mortality after alloHSCT [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Number of participants with anti-blinatumomab antibody formation [ Time Frame: Approximately 2 years ] [ Designated as safety issue: Yes ]
  • Number of participants with a change in select vital sign and laboratory parameters [ Time Frame: Approximately 2 years ] [ Designated as safety issue: Yes ]
  • Number of Participants with CR/CRh*/CRi within 12 weeks of treatment initiation. [ Time Frame: Approximately 12 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with event Free Survival (EFS) [ Time Frame: Approximately 12 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Blinatumomab steady state concentration (Css) [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • ALLSS scores for participants [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Investigation for mutations in the tumor DNA to predict resistance to blinatumomab treatment [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: December 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: May 2016 (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
  • FLAG ± anthracycline based regimen (such as Idarubicin 10 mg/m2 days 1, 3; fludarabine 30 mg/m2 days 1-5; cytarabine 2g/m2 days 1-5)
  • HiDAC based regimen that utilize doses of cytarabine arabinoside at least 1 g/m2 or greater per day ± anthracycline and/or in combination with other drugs such as native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents
  • High-dose methotrexate based regimen (such as 500 mg/m2 - 3 g/m2 HDMTX (infusion time up to 24 hours) in combination with other drugs such as native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents
  • Clofarabine or clofarabine based regimens

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 83 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02013167     History of Changes
Other Study ID Numbers: 00103311
Study First Received: December 3, 2013
Last Updated: July 30, 2014
Health Authority: Australia: Therapeutic Goods Administration
Australia: Institutional Ethical Committee
United States: Institutional Review Board
United States: Food and Drug Administration
Czech Republic: Státní ústav pro kontrolu léciv (SUKL)
France: Agence nationale de sécurité du medicament et des produits de santé (ANSM)
Spain: Agencia Española de Medicamentos y Productos Sanitarios (AEM)
Austria: Bundesamt für Sicherheit im Gesundheitswesen /AGES Medizinmarktaufsicht
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Russia: The Ministry of Healthcare of the Russian Federation (Minzdrav)
Italy: Agenzia Italiana del Farmaco (AIFA)
Greece: Ministry of Health & Social Solidarity National Organization for Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Turkey: The Republic of Turkey Ministry of Health
Germany: Paul-Ehrlich-Institut (PEI)
Bulgaria: The Bulgarian Drug Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Ireland: Irish Medicines Board (IMB)
Israel: Ministry of Health

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

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

ClinicalTrials.gov processed this record on September 18, 2014