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

21 april 2016 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

43

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Australien
      • Herston, Australien
        • Teva Investigational Site 300
      • Parkville, Australien
        • Teva Investigational Site 301
      • Randwick, Australien
        • Teva Investigational Site 302
  • Belarus
      • Minsk, Belarus
        • Teva Investigational Site 520
  • Brasilien
      • Barretos-SP, Brasilien
        • Teva Investigational Site 615
      • Caxias do Sul, Brasilien
        • Teva Investigational Site 616
      • Curitiba-PR, Brasilien
        • Teva Investigational Site 613
      • Porto Alegre, Brasilien
        • Teva Investigational Site 612
      • Porto Alegre, Brasilien
        • Teva Investigational Site 614
      • Sao Paulo, Brasilien
        • Teva Investigational Site 610
      • Sao Paulo, Brasilien
        • Teva Investigational Site 611
      • Sao Paulo-SP, Brasilien
        • Teva Investigational Site 617
  • Förenta staterna
    • California
      • Orange, California, Förenta staterna
        • Teva Investigational Site 17
      • San Diego, California, Förenta staterna
        • Teva Investigational Site 12
    • Florida
      • St. Petersburg, Florida, Förenta staterna
        • Teva Investigational Site 10
    • Maryland
      • Baltimore, Maryland, Förenta staterna
        • Teva Investigational Site 8
    • Massachusetts
      • Boston, Massachusetts, Förenta staterna
        • Teva Investigational Site 16
    • Michigan
      • Detroit, Michigan, Förenta staterna
        • Teva Investigational Site 9
    • Mississippi
      • Jackson, Mississippi, Förenta staterna
        • Teva Investigational Site 1
    • Missouri
      • Kansas City, Missouri, Förenta staterna
        • Teva Investigational Site 5
      • St. Louis, Missouri, Förenta staterna
        • Teva Investigational Site 14
    • New York
      • New York, New York, Förenta staterna
        • Teva Investigational Site 15
    • Oregon
      • Portland, Oregon, Förenta staterna
        • Teva Investigational Site 18
    • Pennsylvania
      • Hershey, Pennsylvania, Förenta staterna
        • Teva Investigational Site 11
      • Philadelphia, Pennsylvania, Förenta staterna
        • Teva Investigational Site 7
    • Tennessee
      • Memphis, Tennessee, Förenta staterna
        • Teva Investigational Site 19
    • Texas
      • Dallas, Texas, Förenta staterna
        • Teva Investigational Site 3
      • Fort Worth, Texas, Förenta staterna
        • Teva Investigational Site 4
      • Houston, Texas, Förenta staterna
        • Teva Investigational Site 13
    • Washington
      • Seattle, Washington, Förenta staterna
        • Teva Investigational Site 2
    • Wisconsin
      • Milwaukee, Wisconsin, Förenta staterna
        • Teva Investigational Site 6
  • Israel
      • Jerusalem, Israel
        • Teva Investigational Site 501
      • Petach Tikva, Israel
        • Teva Investigational Site 503
      • Ramat Gan, Israel
        • Teva Investigational Site 502
  • Kanada
      • Toronto, Kanada
        • Teva Investigational Site 100
  • Korea, Republiken av
      • Seoul, Korea, Republiken av
        • Teva Investigational Site 330
      • Seoul, Korea, Republiken av
        • Teva Investigational Site 331
      • Seoul, Korea, Republiken av
        • Teva Investigational Site 332
      • Seoul, Korea, Republiken av
        • Teva Investigational Site 333
  • Mexiko
      • Guadalajara, Mexiko
        • Teva Investigational Site 603
      • Mexico City, Mexiko
        • Teva Investigational Site 600
      • Mexico City, Mexiko
        • Teva Investigational Site 601
      • Monterrey, Mexiko
        • Teva Investigational Site 602
  • Nya Zeeland
      • Auckland, Nya Zeeland
        • Teva Investigational Site 303
  • Polen
      • Bialystok, Polen
        • Teva Investigational Site 531
      • Lublin, Polen
        • Teva Investigational Site 530
      • Warszawa, Polen
        • Teva Investigational Site 532
  • Ryska Federationen
      • Moscow, Ryska Federationen
        • Teva Investigational Site 511
      • St. Petersburg, Ryska Federationen
        • Teva Investigational Site 510
  • Singapore
      • Singapore, Singapore
        • Teva Investigational Site 320

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

1 år till 20 år (Barn, Vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: Bendamustine

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Recommended Phase II Dose (RP2D) of Bendamustine
Tidsram: Induction Cycle (21- to 35-day cycle)
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.
Induction Cycle (21- to 35-day cycle)
Overall Response Rate (ORR)
Tidsram: Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
Assessed at each treatment cycle (21 to 35 days), for a maximum of 12 cycles

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Best Overall Tumor Response Rate
Tidsram: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Best Overall Tumor Response Rate, by Phase
Tidsram: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Duration of Response (DOR)
Tidsram: At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
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.
At each treatment cycle (21 to 35 days), for a maximum of 12 cycles
Maximum Observed Plasma Drug Concentration (Cmax) for Bendamustine and Its Metabolites (M3 and M4)
Tidsram: 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.
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.
Time to Maximum Plasma Drug Concentration (Tmax) for Bendamustine and Its Metabolites (M3 and M4)
Tidsram: 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.
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.
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)
Tidsram: 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.
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.
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)
Tidsram: 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.
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.

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 augusti 2010

Primärt slutförande (Faktisk)

1 augusti 2011

Avslutad studie (Faktisk)

1 augusti 2011

Studieregistreringsdatum

Först inskickad

16 mars 2010

Först inskickad som uppfyllde QC-kriterierna

16 mars 2010

Första postat (Uppskatta)

18 mars 2010

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

23 maj 2016

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

21 april 2016

Senast verifierad

1 april 2016

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • C18083/2046
  • 2010-020768-40 (EudraCT-nummer)

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