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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01088984




Registration number
NCT01088984
Ethics application status
Date submitted
16/03/2010
Date registered
18/03/2010
Date last updated
23/05/2016

Titles & IDs
Public title
Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
Scientific title
An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
Secondary ID [1] 0 0
2010-020768-40
Secondary ID [2] 0 0
C18083/2046
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Bendamustine - Bendamustine 90 or 120 mg/m\^2 administered as an intravenous (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.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase II Dose (RP2D) of Bendamustine
Timepoint [1] 0 0
Induction Cycle (21- to 35-day cycle)
Primary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Secondary outcome [1] 0 0
Best Overall Tumor Response Rate
Timepoint [1] 0 0
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Secondary outcome [2] 0 0
Best Overall Tumor Response Rate, by Phase
Timepoint [2] 0 0
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Secondary outcome [4] 0 0
Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
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)
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
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.

Eligibility
Key inclusion criteria
Key

* The patient has histologically proven acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) that has relapsed or is refractory to the last regimen, and the patient is without alternative curative therapy.
* The patient's last myelosuppression therapy ended at least 2 weeks before the first dose of study drug.
* Nonhematologic acute toxic effects of prior therapy have resolved to grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
* The patient has adequate liver function with bilirubin values less than or equal to 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values less than or equal to 5 times the age-appropriate ULN.
* The patient has adequate renal function with serum creatinine values less than 2 times ULN.
* The patient has Karnofsky or Lansky performance status of 60 or greater. Patients older than 16 years of age will be scored according to the Karnofsky scale and patients 16 years of age or younger will be scored according to the Lansky scale.
* The patient may have had hematopoietic stem cell transplantation.
* Women of childbearing potential (not surgically sterile) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
* Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
* The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.

Key
Minimum age
1 Year
Maximum age
20 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* The patient has any active, uncontrolled systemic infection, severe concurrent disease, or symptomatic untreated central nervous system (CNS) involvement.
* The patient has evidence of active graft versus host disease.
* The patient has a known human immunodeficiency virus (HIV) infection.
* The patient has active hepatitis B or hepatitis C infection.
* The patient is a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study immediately.
* The patient has any serious uncontrolled medical or psychological disorder that would impair the ability of the patient to receive study drug.
* The patient has any condition that places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.
* The patient has received any other investigational agent within 30 days of study entry.
* The patient has known hypersensitivity to bendamustine or mannitol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2011
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Teva Investigational Site 300 - Herston
Recruitment hospital [2] 0 0
Teva Investigational Site 301 - Parkville
Recruitment hospital [3] 0 0
Teva Investigational Site 302 - Randwick
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Mississippi
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Belarus
State/province [15] 0 0
Minsk
Country [16] 0 0
Brazil
State/province [16] 0 0
Barretos-SP
Country [17] 0 0
Brazil
State/province [17] 0 0
Caxias do Sul
Country [18] 0 0
Brazil
State/province [18] 0 0
Curitiba-PR
Country [19] 0 0
Brazil
State/province [19] 0 0
Porto Alegre
Country [20] 0 0
Brazil
State/province [20] 0 0
Sao Paulo-SP
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Canada
State/province [22] 0 0
Toronto
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Petach Tikva
Country [25] 0 0
Israel
State/province [25] 0 0
Ramat Gan
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Mexico
State/province [27] 0 0
Guadalajara
Country [28] 0 0
Mexico
State/province [28] 0 0
Mexico City
Country [29] 0 0
Mexico
State/province [29] 0 0
Monterrey
Country [30] 0 0
New Zealand
State/province [30] 0 0
Auckland
Country [31] 0 0
Poland
State/province [31] 0 0
Bialystok
Country [32] 0 0
Poland
State/province [32] 0 0
Lublin
Country [33] 0 0
Poland
State/province [33] 0 0
Warszawa
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Moscow
Country [35] 0 0
Russian Federation
State/province [35] 0 0
St. Petersburg
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Teva Branded Pharmaceutical Products R&D, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of phase 1 of this study is to establish the recommended phase II dose (RP2D). The primary objective of phase 2 of this study is to evaluate the safety and efficacy of bendamustine at the recommended pediatric dose for the treatment of pediatric patients with relapsed or refractory acute leukemia.
Trial website
https://clinicaltrials.gov/study/NCT01088984
Trial related presentations / publications
Fraser C, Brown P, Megason G, Ahn HS, Cho B, Kirov I, Frankel L, Aplenc R, Bensen-Kennedy D, Munteanu M, Weaver J, Harker-Murray P. Open-label bendamustine monotherapy for pediatric patients with relapsed or refractory acute leukemia: efficacy and tolerability. J Pediatr Hematol Oncol. 2014 May;36(4):e212-8. doi: 10.1097/MPH.0000000000000021.
Public notes

Contacts
Principal investigator
Name 0 0
Sponsor's Medical Expert
Address 0 0
Cephalon
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01088984