Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
21. dubna 2016 aktualizováno: Teva Branded Pharmaceutical Products R&D, Inc.
An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia
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.
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
43
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Herston, Austrálie
- Teva Investigational Site 300
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Parkville, Austrálie
- Teva Investigational Site 301
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Randwick, Austrálie
- Teva Investigational Site 302
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Barretos-SP, Brazílie
- Teva Investigational Site 615
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Caxias do Sul, Brazílie
- Teva Investigational Site 616
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Curitiba-PR, Brazílie
- Teva Investigational Site 613
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Porto Alegre, Brazílie
- Teva Investigational Site 612
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Porto Alegre, Brazílie
- Teva Investigational Site 614
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Sao Paulo, Brazílie
- Teva Investigational Site 610
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Sao Paulo, Brazílie
- Teva Investigational Site 611
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Sao Paulo-SP, Brazílie
- Teva Investigational Site 617
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Minsk, Bělorusko
- Teva Investigational Site 520
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Jerusalem, Izrael
- Teva Investigational Site 501
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Petach Tikva, Izrael
- Teva Investigational Site 503
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Ramat Gan, Izrael
- Teva Investigational Site 502
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Toronto, Kanada
- Teva Investigational Site 100
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Seoul, Korejská republika
- Teva Investigational Site 330
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Seoul, Korejská republika
- Teva Investigational Site 331
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Seoul, Korejská republika
- Teva Investigational Site 332
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Seoul, Korejská republika
- Teva Investigational Site 333
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Guadalajara, Mexiko
- Teva Investigational Site 603
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Mexico City, Mexiko
- Teva Investigational Site 600
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Mexico City, Mexiko
- Teva Investigational Site 601
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Monterrey, Mexiko
- Teva Investigational Site 602
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Auckland, Nový Zéland
- Teva Investigational Site 303
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Bialystok, Polsko
- Teva Investigational Site 531
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Lublin, Polsko
- Teva Investigational Site 530
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Warszawa, Polsko
- Teva Investigational Site 532
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Moscow, Ruská Federace
- Teva Investigational Site 511
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St. Petersburg, Ruská Federace
- Teva Investigational Site 510
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Singapore, Singapur
- Teva Investigational Site 320
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California
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Orange, California, Spojené státy
- Teva Investigational Site 17
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San Diego, California, Spojené státy
- Teva Investigational Site 12
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Florida
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St. Petersburg, Florida, Spojené státy
- Teva Investigational Site 10
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Maryland
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Baltimore, Maryland, Spojené státy
- Teva Investigational Site 8
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Massachusetts
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Boston, Massachusetts, Spojené státy
- Teva Investigational Site 16
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Michigan
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Detroit, Michigan, Spojené státy
- Teva Investigational Site 9
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Mississippi
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Jackson, Mississippi, Spojené státy
- Teva Investigational Site 1
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Missouri
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Kansas City, Missouri, Spojené státy
- Teva Investigational Site 5
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St. Louis, Missouri, Spojené státy
- Teva Investigational Site 14
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New York
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New York, New York, Spojené státy
- Teva Investigational Site 15
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Oregon
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Portland, Oregon, Spojené státy
- Teva Investigational Site 18
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Pennsylvania
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Hershey, Pennsylvania, Spojené státy
- Teva Investigational Site 11
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Philadelphia, Pennsylvania, Spojené státy
- Teva Investigational Site 7
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Tennessee
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Memphis, Tennessee, Spojené státy
- Teva Investigational Site 19
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Texas
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Dallas, Texas, Spojené státy
- Teva Investigational Site 3
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Fort Worth, Texas, Spojené státy
- Teva Investigational Site 4
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Houston, Texas, Spojené státy
- Teva Investigational Site 13
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Washington
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Seattle, Washington, Spojené státy
- Teva Investigational Site 2
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Wisconsin
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Milwaukee, Wisconsin, Spojené státy
- Teva Investigational Site 6
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
1 rok až 20 let (Dítě, Dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: 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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Recommended Phase II Dose (RP2D) of Bendamustine
Časové okno: Induction Cycle (21- to 35-day cycle)
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RP2D was determined by a traditional 3+3 dose escalation design, with the following restrictions: only doses of 60, 90, 120, and 150 mg/m^2 were explored, and escalation to 150 mg/m^2 would only occur if the 120 mg/m^2 dose was deemed safe and pharmacokinetic data indicate subtherapeutic exposure as compared with adults.
The first cohort was administered bendamustine at the 90 mg/m^2 dose; de-escalation to the 60 mg/m^2 dose would only occur if the starting dose led to dose-limiting toxicity (DLT) in 2 or more participants.
A DLT was defined as any study drug-related nonhematologic adverse event (AE) that was grade 4 for toxicity by National Cancer Institute's Common Toxicity Criteria for AEs, version 4. In addition, grade 3 or above allergic reaction or skin rash were considered DLTs.
Hematologic AEs were not considered DLTs.
The dose level at which at least 2 of 3 or 2 of 6 participants had a DLT was considered as exceeding the RP2D.
The RP2D was the dose 1 step below that level.
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Induction Cycle (21- to 35-day cycle)
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Overall Response Rate (ORR)
Časové okno: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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ORR was calculated as follows: number of participants in the primary analysis set achieving a best overall response of complete remission without platelet recovery (CRp) or complete remission (CR), divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A CR required no evidence of circulating blasts or extramedullary disease, an M1 marrow (≤ 5% bone marrow blasts), and recovery of peripheral counts (platelets ≥ 100 × 10^9/L and absolute neutrophil count ≥ 1.0 × 10^9/L).
A CR without platelet recovery (CRp) required all of the criteria for a CR with the exception of platelet recovery.
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Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Best Overall Tumor Response Rate
Časové okno: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Best Overall Tumor Response Rate, by Phase
Časové okno: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Biological activity of bendamustine was defined as achieving a best response of partial response (PR), CRp, or CR.
Rate was calculated as follows: number of participants in the primary analysis set achieving a best overall response of PR, CRp, or CR, divided by the number of participants in the primary analysis set.
The most positive response for each patient during the study was counted.
The 95% CI was calculated using binomial parameter exact method.
Response was determined by the investigator, and evaluated per Jeha et al, 2006: A PR had to meet the following criteria: complete disappearance of circulating blasts and an M2 marrow (≥ 5% and ≤ 25% bone marrow blasts) and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp.
See Outcome Measure 2 for full definitions for CRp and CR.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Duration of Response (DOR)
Časové okno: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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DOR was determined for the participants with CR or CRp in the primary analysis set, defined as the time from first achieving remission to the time when progression was diagnosed, the participant died, or the participant started receiving new antineoplastic therapy.
Data from participants who do not progress were censored at the last valid assessments.
Median DOR and its 95% confidence interval was determined based on the Kaplan-Meier method.
Data from participants who received a transplant were censored at the time of the transplant.
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At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Časové okno: 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.
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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.
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Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Časové okno: 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.
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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.
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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)
Časové okno: 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.
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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.
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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)
Časové okno: 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.
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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.
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. srpna 2010
Primární dokončení (Aktuální)
1. srpna 2011
Dokončení studie (Aktuální)
1. srpna 2011
Termíny zápisu do studia
První předloženo
16. března 2010
První předloženo, které splnilo kritéria kontroly kvality
16. března 2010
První zveřejněno (Odhad)
18. března 2010
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
23. května 2016
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
21. dubna 2016
Naposledy ověřeno
1. dubna 2016
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- C18083/2046
- 2010-020768-40 (Číslo EudraCT)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .