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Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

2. oktober 2018 opdateret af: Celgene

A Phase 2, Multi-Center, Randomized, Double-Blinded, Parallel Group Study of the Safety and Efficacy of Different Lenalidomide (REVLIMID®) Dose Regimens in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

104

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre
  • Det Forenede Kongerige
      • Leeds, Det Forenede Kongerige, LS9 7TF
        • St James's Institute of Oncology
      • London, Det Forenede Kongerige, SE5 9RS
        • King's College Hospital
      • London, Det Forenede Kongerige, SW3 6JJ
        • The Royal Marsden Hospital
      • London, Det Forenede Kongerige, EC1M 6BQ
        • St.Bartholomew's Hospital
      • Manchester, Det Forenede Kongerige, M20 4BX
        • Christie Hospital NHS Foundation Trust
  • Forenede Stater
    • California
      • La Jolla, California, Forenede Stater, 92093-0820
        • UCSD Moores Cancer Center
      • Rancho Mirage, California, Forenede Stater, 92270
        • Desert Hematology Oncology Medical Group, Inc.
      • Stanford, California, Forenede Stater, 94305-5821
        • Stanford University School of Medicine
    • Connecticut
      • Southington, Connecticut, Forenede Stater, 06489
        • Cancer Center of Central Connecticut
    • Florida
      • Lecanto, Florida, Forenede Stater, 34461
        • Cancer and Blood Disease Center
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60612
        • Rush University Medical Center
      • Chicago, Illinois, Forenede Stater, 60611-2927
        • Northwestern University Medical Center Division of Hematology Oncology
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202-5149
        • Indiana University Cancer Center
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Karmanos Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, Forenede Stater, 14263
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, Forenede Stater, 11042
        • Long Island Jewish Medical Center CLL Research and Treatment Program
    • North Carolina
      • Winston-Salem, North Carolina, Forenede Stater, 27104
        • Wake Forest University School of Medicine
    • Ohio
      • Canton, Ohio, Forenede Stater, 44718
        • Gabrail Cancer Center Research
      • Cleveland, Ohio, Forenede Stater, 44195
        • Cleveland Clinic Foundation
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19102
        • Drexel University, College of Medicine, Clinical Research Group
  • Frankrig
      • Amiens, Frankrig, 80054
        • CHU Sud
      • Bobigny Cedex, Frankrig, 93009
        • Hopital Avicenne
      • Grenoble Cedex 09, Frankrig, 38043
        • Chu Grenoble
      • Le Mans, Frankrig, 72000
        • Clinique Victor Hugo
      • Marseille Cedex 9, Frankrig, 13273
        • Institut Paoli Calmettes
      • Montpellier Cedex 5, Frankrig, 34295
        • CHU Montpellier - Hôpital Saint Eloi
      • Mulhouse, Frankrig, 68000
        • Hopital Emile Muller
      • Paris, Frankrig, 75651
        • Hôpital Pitie Salpétrière
      • Perpignan, Frankrig, 66046
        • CH Perpignan - Hopital Saint-Jean
      • Pessac, Frankrig, 33604
        • CHRU - Hôpital du Haut Lévêque
      • Pierre Bénite, Frankrig, 69310
        • Centre Hospitalier LYON SUD
      • REIMS cedex, Frankrig, 51092
        • Hopital Robert Debre
      • Rennes cedex, Frankrig, 35033
        • CHU Rennes Hematology
      • Vandoeuvre les Nancy, Frankrig, 54511
        • CHRU Hopital Brabois
  • Italien
      • Genova, Italien, 16132
        • Azienda Ospedaliera Universitaria San Martino
      • Lecce, Italien, 73100
        • Ematologia ed Immunologia, Azienda Ospedaliera "Vito Fazzi" di Lecce
      • Milano, Italien, 20141
        • Istituto Europeo Di Oncologia - IEO
      • Milano, Italien, 20132
        • I.R.C.C.S. Ospedale San Raffaele
      • Padova, Italien, 35128
        • Universita Degli Studi Di Padova
      • Perugia, Italien, 06100
        • Universita' degli Studi di Perugia
  • Spanien
      • Barcelona, Spanien, 08916
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spanien, 08036
        • Hospital Clinic Provincial De Barcelona
  • Sverige
      • Stockholm, Sverige, 14186
        • Karolinska Universitetssjukhuset
  • Tyskland
      • Berlin, Tyskland, 13353
        • Charité -Universitätsmedizin Berlin
      • Essen, Tyskland, 45122
        • Universitätsklinikum Essen
      • Greifswald, Tyskland, 17487
        • Ernst-Moritz-Arndt-Universität Greifswald
      • Kiel, Tyskland, 24116
        • Universitatsklinikum Schleswig Holstein
      • Köln, Tyskland, 50924
        • Klinikum der Universität zu Köln
      • Ulm, Tyskland, 89081
        • University of Ulm Abteilung Innere Medizin III

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

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Age ≥ 18 years at the time of signing the informed consent form
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Must have a documented diagnosis of B-cell CLL
  • Must be relapsed or refractory to at least 1 regimen for treatment of CLL. At least one of the prior treatments must have included a purine analog-based or bendamustine-based regimen
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Active infections requiring systemic antibiotics
  • Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide treatment
  • Alemtuzumab therapy within 120 days of initiating lenalidomide treatment
  • Prior therapy with lenalidomide
  • History of grade 4 rash due to prior thalidomide treatment
  • Planned autologous or allogeneic bone marrow transplantation
  • Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
  • Uncontrolled hyperthyroidism or hypothyroidism
  • Venous thromboembolism within 12 months
  • ≥ Grade 2 neuropathy
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]
  • Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy

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: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Lenalidomide 5 mg

Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug
Medicin: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity
Eksperimentel: Lenalidomide 10 mg

Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug
Medicin: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity
Eksperimentel: Lenalidomide 15 mg

Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug
Medicin: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Treatment-emergent Adverse Events
Tidsramme: From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.
Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event.
From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Response Rate (ORR)
Tidsramme: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils >1.5 x 10^9/L, platelets >100 x 10^9/L, hemoglobin (hgb) >11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a ≥ 50% reduction in lymphadenopathy or ≥50% reduction of liver enlargement or ≥50% reduction of spleen enlargement plus neutrophils >1.5 x 10^9/ or ≥50% increase, platelets >100 x 10^9/L or ≥50% increase, hgb 11 g/dL.
Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
Kaplan-Meier Estimate of Duration of Response
Tidsramme: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression.
Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
Time to Response
Tidsramme: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period.
Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
Kaplan-Meier Estimate of Time to Progression
Tidsramme: From randomization until the end of the study; maximum time on study was 91 months.
Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression.
From randomization until the end of the study; maximum time on study was 91 months.
Kaplan-Meier Estimate of Event-Free Survival
Tidsramme: From randomization until the end of the study; maximum time on study was 91 months.
Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
From randomization until the end of the study; maximum time on study was 91 months.
Kaplan-Meier Estimate of Progression Free Survival
Tidsramme: From randomization until the end of the study; maximum time on study was 91 months.
Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
From randomization until the end of the study; maximum time on study was 91 months.
Kaplan-Meier Estimate of Overall Survival
Tidsramme: From randomization until the end of the study; maximum time on study was 91 months.
Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented.
From randomization until the end of the study; maximum time on study was 91 months.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Celgene

Efterforskere

  • Studieleder: Jeffery Jones, M.D., MPH, Celgene Corporation

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.

Generelle publikationer

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 (Faktiske)

19. oktober 2009

Primær færdiggørelse (Faktiske)

5. september 2017

Studieafslutning (Faktiske)

5. september 2017

Datoer for studieregistrering

Først indsendt

20. august 2009

Først indsendt, der opfyldte QC-kriterier

20. august 2009

Først opslået (Skøn)

21. august 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

31. oktober 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

2. oktober 2018

Sidst verificeret

1. oktober 2018

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CC-5013-CLL-009
  • 2009-009836-54 (EudraCT nummer)

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 .

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