Try our beta test site

Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01471782
First received: October 28, 2011
Last updated: December 16, 2016
Last verified: December 2016
Results First Received: September 23, 2016  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Acute Lymphoblastic Leukemia
Intervention: Biological: Blinatumomab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted in 26 centers in Germany, France, Italy, the Netherlands, the United Kingdom, and the United States of America. Results are reported for the primary analysis with a data cut-off date of 12 January 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

The Phase 1 part of the study comprised 2 parts:

  • a dose evaluation/escalation part in patients aged 2 to 17 years to define the recommended phase 2 dose of blinatumomab (4 arms),
  • a pharmacokinetic (PK) expansion part in patients less than 18 years.

The Phase 2 efficacy part enrolled patients at the recommended dose determined in phase 1.


Reporting Groups
  Description
Phase 1: Blinatumomab 5 µg/m²/Day Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 15 µg/m²/Day Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 30 µg/m²/Day Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 15/30 µg/m²/Day Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Phase 1: Blinatumomab 5/15 µg/m²/Day PK Expansion: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Phase 2: Blinatumomab 5/15 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.

Participant Flow:   Overall Study
    Phase 1: Blinatumomab 5 µg/m²/Day   Phase 1: Blinatumomab 15 µg/m²/Day   Phase 1: Blinatumomab 30 µg/m²/Day   Phase 1: Blinatumomab 15/30 µg/m²/Day   Phase 1: Blinatumomab 5/15 µg/m²/Day   Phase 2: Blinatumomab 5/15 µg/m²/Day
STARTED   5   7   5   6   26   44 
COMPLETED   0 [1]   1 [1]   0 [1]   1 [1]   0 [1]   3 [1] 
NOT COMPLETED   5   6   5   5   26   41 
Hematopoietic Stem Cell Transplantation                2                2                1                0                5                3 
Lack of Efficacy                1                2                1                1                5                18 
Adverse Event                1                1                2                2                3                1 
Other                0                0                1                1                6                5 
Change of Chemotherapy                1                1                0                0                1                4 
Disease Relapse                0                0                0                1                2                1 
Physician Decision                0                0                0                0                3                8 
Withdrawal by Parent/Guardian                0                0                0                0                1                0 
Death                0                0                0                0                0                1 
[1] Completed 5 cycles



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase 1: Blinatumomab 5 µg/m²/Day Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 15 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 30 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Phase 1: Blinatumomab 15/30 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Phase 1: Blinatumomab 5/15 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Phase 2: Blinatumomab 5/15 µg/m²/Day Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Total Total of all reporting groups

Baseline Measures
   Phase 1: Blinatumomab 5 µg/m²/Day   Phase 1: Blinatumomab 15 µg/m²/Day   Phase 1: Blinatumomab 30 µg/m²/Day   Phase 1: Blinatumomab 15/30 µg/m²/Day   Phase 1: Blinatumomab 5/15 µg/m²/Day   Phase 2: Blinatumomab 5/15 µg/m²/Day   Total 
Overall Participants Analyzed 
[Units: Participants]
 5   7   5   6   26   44   93 
Age, Customized 
[Units: Participants]
             
< 2 years   0   0   0   0   8   2   10 
2 - 6 years   3   5   2   4   9   11   34 
7 - 17 years   2   2   3   2   9   31   49 
Gender 
[Units: Participants]
Count of Participants
             
Female      3  60.0%      4  57.1%      2  40.0%      1  16.7%      11  42.3%      12  27.3%      33  35.5% 
Male      2  40.0%      3  42.9%      3  60.0%      5  83.3%      15  57.7%      32  72.7%      60  64.5% 
Race/Ethnicity, Customized [1] 
[Units: Participants]
             
White   5   7   5   5   22   33   77 
Asian   0   0   0   0   0   0   0 
Black or African American   0   0   0   0   0   0   0 
American Indian or Alaska native   0   0   0   0   0   0   0 
Native Hawaiian or other Pacific islander   0   0   0   0   0   0   0 
Other   0   0   0   1   3   5   9 
Unknown   0   0   0   0   1   6   7 
[1] Race was not recorded for any patient from France and for two further patients.
Prior Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) 
[Units: Participants]
             
Yes   3   6   2   4   15   25   55 
No   2   1   3   2   11   19   38 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase I: Number of Participants With Dose-limiting Toxicities (DLTs)   [ Time Frame: Cycle 1, 28 days ]

2.  Primary:   Percentage of Participants With Complete Remission in the First Two Cycles   [ Time Frame: Cycles 1 and 2 (12 weeks) ]

3.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 28 days ]

4.  Secondary:   Steady State Concentration of Blinatumomab   [ Time Frame: Cycles 1 and 2 during the IV infusion on day 3 (at least 48 hours after start of infusion) and days 8, 15 and 22 (steady state) and day 29 at End of Infusion (EoI) and 2, 4, and 8 hours after EoI for ages ≥ 2 years. ]

5.  Secondary:   Time to Hematological Relapse (Duration of Response)   [ Time Frame: Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2. ]

6.  Secondary:   Overall Survival   [ Time Frame: Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.6 months for phase 2. ]

7.  Secondary:   Relapse-free Survival   [ Time Frame: Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2. ]

8.  Secondary:   Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant During Blinatumomab Induced Remission   [ Time Frame: Up to the data cut-off date of 12 January 2015; Maximum duration on study was 24 months in phase 1 and 15 months for phase 2. ]

9.  Secondary:   Number of Participants Who Developed Anti-blinatumomab Antibodies   [ Time Frame: Predose up until 30 days after last dose of study medication; median treatment duration was 28 days. ]

10.  Secondary:   Serum Cytokine Peak Levels   [ Time Frame: Cycle 1 and 2 day 1 (prior to infusion, 2 and 6 hours after infusion start), day 2 and day 3. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen, Inc
phone: 866-572-6436



Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01471782     History of Changes
Other Study ID Numbers: MT103-205
2010-024264-18 ( EudraCT Number )
Study First Received: October 28, 2011
Results First Received: September 23, 2016
Last Updated: December 16, 2016