Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

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

21. april 2016 oppdatert 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

43

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

1 år til 20 år (Barn, Voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Legemiddel: Bendamustine

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Recommended Phase II Dose (RP2D) of Bendamustine
Tidsramme: 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)
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Best Overall Tumor Response Rate
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. august 2010

Primær fullføring (Faktiske)

1. august 2011

Studiet fullført (Faktiske)

1. august 2011

Datoer for studieregistrering

Først innsendt

16. mars 2010

Først innsendt som oppfylte QC-kriteriene

16. mars 2010

Først lagt ut (Anslag)

18. mars 2010

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

23. mai 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. april 2016

Sist bekreftet

1. april 2016

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere