Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01088984
First received: March 16, 2010
Last updated: September 24, 2014
Last verified: March 2013
Results First Received: September 24, 2014  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Leukemia
Intervention: Drug: Bendamustine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Of the 46 patients screened, 43 patients at 24 centers from the United States, Australia, South Korea, Israel, Mexico, and Brazil met entry criteria and were considered eligible for enrollment. Of the 3 patients who were not enrolled, 2 patients died prior to study enrollment, and 1 patient was ineligible because inclusion criteria were not met.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Bendamustine 90 mg/m^2 Bendamustine 90 mg/m^2 administered as an intravenous (IV) infusion over 60 minutes on Days 1 and 2 of a 21-day Induction cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Bendamustine 120 mg/m^2 Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (maximum of 12 total cycles), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.

Participant Flow for 2 periods

Period 1:   Phase 1
    Bendamustine 90 mg/m^2     Bendamustine 120 mg/m^2  
STARTED     5     6  
COMPLETED     0 [1]   0 [1]
NOT COMPLETED     5     6  
Death                 2                 1  
Disease Progression                 2                 4  
Not Specified                 1                 1  
[1] completed follow-up up to 12 month from last dose of study drug

Period 2:   Phase 2
    Bendamustine 90 mg/m^2     Bendamustine 120 mg/m^2  
STARTED     0     32  
COMPLETED     0 [1]   0 [1]
NOT COMPLETED     0     32  
Death                 0                 5  
Withdrawal by Subject                 0                 1  
DIsease Progression                 0                 25  
Not Specified                 0                 1  
[1] completed follow-up up to 12 month from last dose of study drug



  Baseline Characteristics
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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.
Includes 5 participants treated with bendamustine at 90 mg/m2 in Phase 1, and 6 participants treated with bendamustine at 120 mg/m2 in Phase 1, and 32 participants treated with the recommended phase II dose (RP2D) of bendamustine (120 mg/m2) in Phase 2.

Reporting Groups
  Description
Phase 1: Bendamustine 90 or 120 mg/m^2 Bendamustine 90 or 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of a 21-day Induction Cycle, with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Phase 2: Bendamustine 120 mg/m^2 Bendamustine 120 mg/m^2 administered as an IV infusion over 60 minutes on Days 1 and 2 of each 21-day cycle (Cycles 2 through 12), with delays up to 2 weeks for neutrophil and platelet count recovery, for up to a 35-day cycle.
Total Total of all reporting groups

Baseline Measures
    Phase 1: Bendamustine 90 or 120 mg/m^2     Phase 2: Bendamustine 120 mg/m^2     Total  
Number of Participants  
[units: participants]
  11     32     43  
Age  
[units: years]
Mean ± Standard Deviation
  8.7  ± 4.31     9.3  ± 4.93     9.2  ± 4.74  
Age, Customized  
[units: participants]
     
1 to 6 years     4     10     14  
7 to 11 years     3     10     13  
12 to 20 years     4     12     16  
Gender  
[units: participants]
     
Female     1     12     13  
Male     10     20     30  



  Outcome Measures
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1.  Primary:   Recommended Phase II Dose (RP2D) of Bendamustine   [ Time Frame: Induction Cycle (21- to 35-day cycle) ]

2.  Primary:   Overall Response Rate (ORR)   [ Time Frame: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles ]

3.  Secondary:   Best Overall Tumor Response Rate   [ Time Frame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles ]

4.  Secondary:   Best Overall Tumor Response Rate, by Phase   [ Time Frame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles ]

5.  Secondary:   Duration of Response (DOR)   [ Time Frame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles ]

6.  Secondary:   Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)   [ Time Frame: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2. ]

7.  Secondary:   Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)   [ Time Frame: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2. ]

8.  Secondary:   Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until the Last Measurable Plasma Concentration (AUC0-t) for Bendamustine and Its Metabolites (M3 and M4)   [ Time Frame: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2. ]

9.  Secondary:   Area Under the Plasma Drug Concentration by Time Curve From Time 0 Until 24 Hours After Study Drug Administration (AUC0-24) for Bendamustine and Its Metabolites (M3 and M4)   [ Time Frame: Cycle 1, Day 1: before infusion, immediately following the infusion, and 3, 6, 10(±2), and 24 hours after the start of infusion. The 24-hour postinfusion sample was obtained before the start of the infusion on Day 2. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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: Manager
Organization: Teva Pharmaceuticals USA
phone: 1-866-384-5525
e-mail: clinicaltrialqueries@tevausa.com


Publications:

Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01088984     History of Changes
Other Study ID Numbers: C18083/2046, 2010-020768-40
Study First Received: March 16, 2010
Results First Received: September 24, 2014
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belarus: Ministry of Health
Brazil: Ministry of Health
Canada: Health Canada
Israel: Israeli Health Ministry Pharmaceutical Administration
Mexico: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)