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Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstrom's Macroglobulinemia

20 de julho de 2017 atualizado por: German CLL Study Group

Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenström's macroglobulinemia.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

OBJECTIVES:

Primary

  • Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia).

Secondary

  • Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen.
  • Determine event-free and overall survival of patients treated with this regimen.
  • Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen.
  • Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

  • Cytoreductive therapy: Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 (with or without rituximab IV on day 1). Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction.
  • Conditioning regimen: Patients receive 1 of the following conditioning regimens*:

NOTE: *Patients who did not achieve partial response after cytoreductive therapy receive regimen 3.

  • Regimen 1: Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3. If stem cells are collected from an unrelated donor, patients also receive anti-thymocyte globulin (ATG) IV on days -4 to -1.
  • Regimen 2: Patients undergo total-body irradiation on day -9. Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2.

  • Regimen 3: Patients receive fludarabine IV on days -7 to -3, busulfan IV or orally on days -7 to -5, and cyclophosphamide IV on days -3 to -2. If stem cells are collected from an unrelated donor, patients also receive ATG on days -3 to -1.

    • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily starting on day 5 and continuing until blood count recover.
    • Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100. Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1, 3, and 6 OR oral mycophenolate mofetil twice daily on days 0-50. Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion (DLI).
    • DLI: The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization. Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Tipo de estudo

Intervencional

Inscrição (Real)

100

Estágio

  • Fase 2
  • Fase 1

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, 12200
        • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
      • Essen, Alemanha, 45122
        • Universitaetsklinikum Essen
      • Goettingen, Alemanha, 37075
        • Universitaetsklinikum Goettingen
      • Hamburg, Alemanha, D-20099
        • Asklepios Klinik St. Georg
      • Hannover, Alemanha, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Alemanha, D-69120
        • Universitaets-Kinderklinik Heidelberg
      • Homburg, Alemanha, 66421
        • Universitaetsklinikum des Saarlandes
      • Idar-Oberstein, Alemanha, D-55743
        • Clinic for Bone Marrow Transplantation and Hematology and Oncology
      • Kiel, Alemanha, 24116
        • University Hospital Schleswig-Holstein - Kiel Campus
      • Leipzig, Alemanha, 04103
        • University Hospital of Leipzig
      • Regensburg, Alemanha, 93053
        • Klinikum der Universitaet Regensburg
      • Ulm, Alemanha, 89081
        • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
  • Canadá
    • Quebec
      • Montreal, Quebec, Canadá, H1T 2M4
        • Maisonneuve-Rosemont Hospital

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 a 65 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia)

    • Must have poor prognostic features and low probability of successful autografting, defined by one of the following criteria:

      • Progressive disease with unfavorable cytogenetics (deletion or mutation of critical regions on chromosomes 11q and/or 17p [p53]; and/or unmutated status of the immunoglobulin V_H gene region; and/or usage of the V_H 3-21 gene), defined as 1 of the following:

        • Doubling of lymphocyte count or nodal involvement within 3 months or less
        • Progressive decline of platelet count and/or hemoglobin values defining Binet stage C disease (or to 50% or less of baseline values within 3 months) not due to immune mechanisms
        • Symptomatic splenomegaly
        • Discomfort or imminent complications due to large tumor masses
        • B symptoms
      • Refractory disease or early relapse (within 12 months) after treatment with a fludarabine-containing regimen
      • Relapsed after autologous stem cell transplant (SCT)
      • Insufficient stem cell harvest for intended autologous SCT
  • Presence of a clonal CDR III rearrangement detected by polymerase chain reaction
  • No Richter's syndrome
  • HLA-identical sibling or unrelated donor available

PATIENT CHARACTERISTICS:

  • ECOG performance status ≤ 1
  • Creatinine clearance > 60 mL/min
  • SGOT, SGPT, and bilirubin < 2 times normal
  • Normal cardiac function determined by ECG and echocardiographic examination
  • Inspiratory vital capacity, FEV_1, and DLCO > 50% of predicted
  • No serious localized or systemic infections
  • No other concurrent malignant disease
  • No impaired organ function
  • No uncontrolled diabetes
  • No uncontrolled hypertension
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No HIV infection
  • No hepatitis B or C infection
  • No concurrent alcohol or drug abuse
  • No dementia or altered mental status that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

  • Not specified

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: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Allogeneic stem cell transplantation

  1. Cytoreductive therapy for inducing a state of partial remission:

    FC or FC-R or alternative salvage regimens (e.g. Alemtuzumab)

  2. Conditioning regimen:

    FC +/- ATG (Arm A) or FC/Busulfan +/- ATG (Arm C: refractory patients only)

  3. allogeneic-PBSCT (from HLA-identical donor)
  4. GVHD prophylaxis: CSA + MTX or MMF
  5. +/- DLI (Donor lymphocyte infusions)
Medicamento: ciclofosfamida
Radiação: radioterapia
Medicamento: metotrexato
Biológico: globulina anti-timócito
Biológico: linfócitos alogênicos terapêuticos
Medicamento: fosfato de fludarabina
Medicamento: busulfan
Procedimento: transplante de células-tronco do sangue periférico
Biológico: filgrastim
Biológico: rituximabe
Biológico: alentuzumabe
Medicamento: ciclosporina
Medicamento: micofenolato mofetil

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Feasibility as measured by the proportion of eligible patients completing the transplant procedure successfully
Safety as measured by a treatment-related mortality of < 25% at 2 years following transplant

Medidas de resultados secundários

Medida de resultado
Clinical remission rate by NIH criteria at 12 months following transplant
Minimal residual disease negativity rate as measured by high-resolution flow or CDR PCR at 12 months following transplant
Chimerism as measured by STR-PCR at 12 months following transplant
Event-free and overall survival at 5 years following transplant

Colaboradores e Investigadores

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

Patrocinador

German CLL Study Group

Investigadores

  • Cadeira de estudo: Peter Dreger, Universitaets-Kinderklinik Heidelberg

Publicações e links úteis

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Publicações Gerais

Links úteis

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

1 de junho de 2000

Conclusão do estudo (Real)

1 de julho de 2010

Datas de inscrição no estudo

Enviado pela primeira vez

24 de janeiro de 2006

Enviado pela primeira vez que atendeu aos critérios de CQ

24 de janeiro de 2006

Primeira postagem (Estimativa)

25 de janeiro de 2006

Atualizações de registro de estudo

Última Atualização Postada (Real)

24 de julho de 2017

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de julho de 2017

Última verificação

1 de abril de 2007

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CLL3X
  • EU-20554
  • MEDAC-FLUD.10/CLL

Plano para dados de participantes individuais (IPD)

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NÃO

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