E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma
22. april 2018 opdateret af: Eisai Co., Ltd.
Phase1/1b Clinical Trial of E7777 for the Treatment of Patients With Peripheral T-Cell Lymphoma
The purpose of this Phase 1 study is to determine the maximum tolerated dose (MTD) through observation of dose limiting toxicity (DLT), which is in advance defined, in patients with peripheral or cutaneous T-cell lymphoma.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
13
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Aichi
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Nagoya, Aichi, Japan
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Chiba
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Kashiwa, Chiba, Japan
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Kanagawa
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Isehara, Kanagawa, Japan
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Tokyo
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Chuo-ku, Tokyo, Japan
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
20 år til 79 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
lnclusion Criteria:
- Male and female patients 20 to less than 80 years of age at the time of informed consent
- Patients histologically or cytologically diagnosed to have peripheral T -cell lymphoma
- Patients with a history of chemotherapy (including PUVA and retinoid) that resulted in relapse, recurrence and treatment resistance (just for the administration of E7777 alone)
- Patients subject to CHOP therapy and without a history of prior treatment with anthracycline or anthraquinone anticancer drugs (just for the administration of E7777 in combination with CHOP therapy)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- No carry-over of beneficial or adverse effects of the prior treatment that may affect the safety evaluation of the investigational drug (excluding Grade 1 neuropathy and alopecia)
Exclusion Criteria:
- Brain metastasis with clinical symptoms which requires treatment
- Serious systemic infection requiring intensive treatment
- Serious complications or histories
- History of hypersensitivity to protein therapeutics
- Known to be positive for HIV antibody, HCV antibody, or HBs antigen
- History of malignancy other than peripheral T-cell lymphoma and less than five years have elapsed since the last remission
- Patients who have undergone allogeneic hematopoietic stem cell transplantation
- Patients with a relapse within 6 months after autologous hematopoietic stem-cell transplantation
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: E7777
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E7777 will be administered by intravenous (IV) infusion for 5 days from Day 1 through 5 of each cycle (21 days/cycle) with 8 cycles in maximum for E7777 alone therapy.
E7777 dose will be escalated from 6 micro-g/kg/day to 12, 15 and then to 18 in a stepwise fashion.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
Tidsramme: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
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The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants.
If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total.
The RD was to be comprehensively determined based on the MTD and safety data.
Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment.
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For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox
Tidsramme: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months
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Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood coagulation, blood chemistry, and urinalysis values; periodic measurement of vital signs, body weight, 12-lead electrocardiograms (ECGs), Eastern Cooperative Oncology Group performance status, physical examination findings, and ophthalmological examination findings.
TEAEs were defined as an AE that had an onset date, or worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to the last assessment.
Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug.
SAEs were defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect.
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From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months
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Maximum Serum Concentration (Cmax) of Denileukin Diftitox
Tidsramme: Cycle 1 (Day 1)
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Cmax was defined as the maximum observed concentration of denileukin diftitox following administration of study treatment on Cycle 1 Day 1 and was obtained directly from the measured serum concentration-time curves.
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a lower limit of quantitation (LLOQ) of 30 nanograms per milliliter (ng/mL).
Serum pharmacokinetic (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the median and full range for all participants and expressed as ng/mL.
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Cycle 1 (Day 1)
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Time to Cmax (Tmax) of Denileukin Diftitox in Serum
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed in minutes.
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Cycle 1 (Day 1)
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Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the median and full range for all participants and expressed as nanograms*minutes per milliliter (ng*min/mL).
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Cycle 1 (Day 1)
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Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf))
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the median and full range for all participants and expressed as ng*min/mL.
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Cycle 1 (Day 1)
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Terminal Phase Rate Constant (λz)
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of λz, which was then summarized as the median and full range for all participants and expressed in 1/minutes.
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Cycle 1 (Day 1)
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Terminal Elimination Phase Half-life (t1/2)
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the median and full range for all participants and expressed in minutes.
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Cycle 1 (Day 1)
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Volume of Distribution at Terminal Phase (Vz)
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vz, which was then summarized as the median and full range for all participants and expressed as milliliters per kilogram (mL/kg).
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Cycle 1 (Day 1)
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Volume of Distribution at Steady State (Vss)
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vss, which was then summarized as the median and full range for all participants and expressed as mL/kg.
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Cycle 1 (Day 1)
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Total Clearance (CL)
Tidsramme: Cycle 1 (Day 1)
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Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox.
The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL.
SerumPK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the median and full range for all participants and expressed as milliliters/minutes/kilograms (mL/min/kg).
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Cycle 1 (Day 1)
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Recommended Dose
Tidsramme: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
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This endpoint was combined with primary outcome measure, MTD
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For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studieleder: Tadashi Nakanishi, Eisai Co., Ltd.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2011
Primær færdiggørelse (Faktiske)
1. august 2015
Studieafslutning (Faktiske)
1. januar 2016
Datoer for studieregistrering
Først indsendt
18. juli 2011
Først indsendt, der opfyldte QC-kriterier
21. juli 2011
Først opslået (Skøn)
25. juli 2011
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
23. november 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
22. april 2018
Sidst verificeret
1. april 2018
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- E7777-J081-101
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .