Clinical trial NCT01088984: Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
Official title: An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2010-03-18
Enrollment: 43
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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 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.

Primary outcomes:
measure: Recommended Phase II Dose (RP2D) of Bendamustine
timeFrame: Induction Cycle (21- to 35-day cycle)
measure: Overall Response Rate (ORR)
timeFrame: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Secondary outcomes:
measure: Best Overall Tumor Response Rate
timeFrame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
measure: Best Overall Tumor Response Rate, by Phase
timeFrame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
measure: Duration of Response (DOR)
timeFrame: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
measure: Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
timeFrame: 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.
measure: Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: 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)
timeFrame: 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.
Other outcomes:
Locations:
city: Orange
country: United States
facility: Teva Investigational Site 17
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 12
state: California
city: St. Petersburg
country: United States
facility: Teva Investigational Site 10
state: Florida
city: Baltimore
country: United States
facility: Teva Investigational Site 8
state: Maryland
city: Boston
country: United States
facility: Teva Investigational Site 16
state: Massachusetts
city: Detroit
country: United States
facility: Teva Investigational Site 9
state: Michigan
city: Jackson
country: United States
facility: Teva Investigational Site 1
state: Mississippi
city: Kansas City
country: United States
facility: Teva Investigational Site 5
state: Missouri
city: St. Louis
country: United States
facility: Teva Investigational Site 14
state: Missouri
city: New York
country: United States
facility: Teva Investigational Site 15
state: New York
city: Portland
country: United States
facility: Teva Investigational Site 18
state: Oregon
city: Hershey
country: United States
facility: Teva Investigational Site 11
state: Pennsylvania
city: Philadelphia
country: United States
facility: Teva Investigational Site 7
state: Pennsylvania
city: Memphis
country: United States
facility: Teva Investigational Site 19
state: Tennessee
city: Dallas
country: United States
facility: Teva Investigational Site 3
state: Texas
city: Fort Worth
country: United States
facility: Teva Investigational Site 4
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 13
state: Texas
city: Seattle
country: United States
facility: Teva Investigational Site 2
state: Washington
city: Milwaukee
country: United States
facility: Teva Investigational Site 6
state: Wisconsin
city: Herston
country: Australia
facility: Teva Investigational Site 300
city: Parkville
country: Australia
facility: Teva Investigational Site 301
city: Randwick
country: Australia
facility: Teva Investigational Site 302
city: Minsk
country: Belarus
facility: Teva Investigational Site 520
city: Barretos-SP
country: Brazil
facility: Teva Investigational Site 615
city: Caxias do Sul
country: Brazil
facility: Teva Investigational Site 616
city: Curitiba-PR
country: Brazil
facility: Teva Investigational Site 613
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 612
city: Porto Alegre
country: Brazil
facility: Teva Investigational Site 614
city: Sao Paulo-SP
country: Brazil
facility: Teva Investigational Site 617
city: Sao Paulo
country: Brazil
facility: Teva Investigational Site 610
city: Sao Paulo
country: Brazil
facility: Teva Investigational Site 611
city: Toronto
country: Canada
facility: Teva Investigational Site 100
city: Jerusalem
country: Israel
facility: Teva Investigational Site 501
city: Petach Tikva
country: Israel
facility: Teva Investigational Site 503
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 502
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 330
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 331
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 332
city: Seoul
country: Korea, Republic of
facility: Teva Investigational Site 333
city: Guadalajara
country: Mexico
facility: Teva Investigational Site 603
city: Mexico City
country: Mexico
facility: Teva Investigational Site 600
city: Mexico City
country: Mexico
facility: Teva Investigational Site 601
city: Monterrey
country: Mexico
facility: Teva Investigational Site 602
city: Auckland
country: New Zealand
facility: Teva Investigational Site 303
city: Bialystok
country: Poland
facility: Teva Investigational Site 531
city: Lublin
country: Poland
facility: Teva Investigational Site 530
city: Warszawa
country: Poland
facility: Teva Investigational Site 532
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 511
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 510
city: Singapore
country: Singapore
facility: Teva Investigational Site 320
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert
role: STUDY_DIRECTOR
References:
citation: 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.