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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 luglio 2017 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

100

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 65 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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)
Droga: ciclofosfamide
Radiazione: radioterapia
Droga: metotrexato
Biologico: globulina antitimocitaria
Biologico: linfociti allogenici terapeutici
Droga: fludarabina fosfato
Droga: busulfan
Procedura: trapianto di cellule staminali del sangue periferico
Biologico: filgrastim
Biologico: rituximab
Biologico: alemtuzumab
Droga: ciclosporina
Droga: micofenolato mofetile

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
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

Misure di risultato secondarie

Misura del risultato
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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

German CLL Study Group

Investigatori

  • Cattedra di studio: Peter Dreger, Universitaets-Kinderklinik Heidelberg

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 giugno 2000

Completamento dello studio (Effettivo)

1 luglio 2010

Date di iscrizione allo studio

Primo inviato

24 gennaio 2006

Primo inviato che soddisfa i criteri di controllo qualità

24 gennaio 2006

Primo Inserito (Stima)

25 gennaio 2006

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 luglio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

20 luglio 2017

Ultimo verificato

1 aprile 2007

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

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

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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