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

2 de outubro de 2018 atualizado por: 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).

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

104

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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
Medicamento: 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
Experimental: 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
Medicamento: 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
Experimental: 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
Medicamento: 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

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Number of Participants With Treatment-emergent Adverse Events
Prazo: 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.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Overall Response Rate (ORR)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Celgene

Investigadores

  • Diretor de estudo: Jeffery Jones, M.D., MPH, Celgene Corporation

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

19 de outubro de 2009

Conclusão Primária (Real)

5 de setembro de 2017

Conclusão do estudo (Real)

5 de setembro de 2017

Datas de inscrição no estudo

Enviado pela primeira vez

20 de agosto de 2009

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de agosto de 2009

Primeira postagem (Estimativa)

21 de agosto de 2009

Atualizações de registro de estudo

Última Atualização Postada (Real)

31 de outubro de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

2 de outubro de 2018

Última verificação

1 de outubro de 2018

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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