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A Study of MabThera (Rituximab) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia.

6. juli 2017 oppdatert av: Hoffmann-La Roche

A Study of Chlorambucil Plus MabThera as Induction Therapy Followed in Responders by Maintenance Therapy Versus Observation on Response Rate in Patients >=60 Years With Previously Untreated Chronic Lymphocytic Leukemia

This single arm study will assess the efficacy and safety of MabThera + chlorambucil as induction therapy, followed in responders by maintenance therapy or observation in elderly patients with previously untreated chronic lymphocytic leukemia. During the induction phase patients will receive 2 x 4 weekly courses of chlorambucil followed by 8 x 4 weekly courses of chlorambucil + MabThera. Subsequently, responders will be randomized to receive 12 doses of MabThera given every 8 weeks, or no further treatment. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

97

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Italia
    • Calabria
      • Catanzaro, Calabria, Italia, 88100
        • Az. Osp. Pugliese; Dh Oncologico
      • Cosenza, Calabria, Italia, 87100
        • P.O. Annunziata; U.O. Ematologia
      • Reggio Calabria, Calabria, Italia, 89100
        • Ospedale Riuniti; Divisione Di Ematologia
    • Campania
      • Napoli, Campania, Italia, 80131
        • Ospedale Cardarelli; Divisione Di Ematologia
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italia, 40138
        • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
      • Ferrara, Emilia-Romagna, Italia, 44100
        • Arcispedale S. Anna; Sezione Di Ematologia
    • Lazio
      • Roma, Lazio, Italia, 00161
        • Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
      • Roma, Lazio, Italia, 00144
        • Ospedale S. Eugenio; Divisione Di Ematologia
    • Liguria
      • Genova, Liguria, Italia, 16132
        • Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
    • Lombardia
      • Milano, Lombardia, Italia, 20122
        • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
      • Milano, Lombardia, Italia, 20162
        • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
    • Piemonte
      • Torino, Piemonte, Italia, 10126
        • A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
      • Torino, Piemonte, Italia, 10126
        • Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
    • Puglia
      • Bari, Puglia, Italia, 70124
        • Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
    • Sicilia
      • Messina, Sicilia, Italia, 98165
        • Az. Osp. Papardo; Struttura Complessa Di Ematologia
      • Via S. Sofia 78, Sicilia, Italia, 95123
        • Ospedale Ferrarotto; Divisione Di Ematologia
    • Toscana
      • Firenze, Toscana, Italia, 50135
        • Az. Osp. Di Careggi; Divisione Di Ematologia
      • Siena, Toscana, Italia, 53100
        • A.O. Universitaria Senese; Ematologia
    • Veneto
      • Padova, Veneto, Italia, 35128
        • Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia
      • Verona, Veneto, Italia, 37134
        • Policlinico G. B. Rossi; Divisione Di Ematologia

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

60 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • adult patients, >=60 years of age;
  • CD20+ chronic lymphocytic leukemia (CLL);
  • no previous treatment for CLL;
  • ECOG performance status 0-1.

Exclusion Criteria:

  • co-morbid conditions requiring long term use of systemic corticosteroids during study treatment;
  • history of severe cardiac disease;
  • transformation to aggressive B-cell malignancy.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 1
Legemiddel: rituximab [MabThera/Rituxan]
375mg/m2 iv on day 1 of course 3; 500mg/m2 iv on day 1 of courses 4-8 (induction phase); 375mg/m2 iv every 8 weeks (maintenance phase).
Legemiddel: chlorambucil
8mg/m2 po on days 1-7 of courses 1-8

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With Documented CR, CRi, or PR at the End of Induction Treatment
Tidsramme: Month 10
CR defined as: 1) laboratory CR: peripheral blood lymphocytes (PBL) less than (<) 4000/microliter (μL), neutrophils (PMN) greater than (>) 1500/μL, platelets >100,000/μL, and hemoglobin (Hb) >11 grams per deciliter (g/dL); 2) clinical CR: lymph nodes (LN) <1.5 centimeter (cm), and no constitutional symptoms, hepatomegaly (HM) or splenomegaly (SM); 3) instrumental CR: LN <1.5 cm and no HM/SM, and 4) bone marrow (BM) CR: normocellular aspirate/biopsy for participant age <30 percent (%) lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to chronic lymphocytic leukemia (CLL), with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from baseline (BL) in the HM/SM, and 1 of the following: PMN >1500/μL, platelets >100,000/μL or >50% improvement from BL, and Hb >11.0 g/dL or >50% improvement from BL.
Month 10

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With Documented CR, CRi, or PR at the End of Study
Tidsramme: Month 35
CR defined as: 1) laboratory CR: PBL <4000/μL, PMN > 1500/μL, platelets > 100,000/μL, and Hb > 11 g/dL; 2) clinical CR: LN < 1.5 cm, and no constitutional symptoms, HM or SM; 3) instrumental CR: LN < 1.5 cm and no HM/SM, and 4) bone marrow CR: normocellular aspirate/biopsy for participant age < 30% lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to CLL, with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from BL in the HM/SM, and 1 of the following: PMN > 1500/μL, platelets > 100,000/μL or > 50% improvement from BL, and Hb >11.0 g/dL or > 50% improvement from BL.
Month 35
Percentage of Participants With CR, CRi, PR, Stable Disease (SD), Progressive Disease (PD), Relapse, or Nodular PR at the End of Induction Treatment
Tidsramme: Month 10
CR, CRi, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a greater than or equal to (≥) 50% increase in greatest diameter of any previously noted lesion; 2) a ≥ 50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥ 50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥ 6 months. Nodular PR was defined by the presence of residual lymphoid nodules.
Month 10
Percentage of Participants With CR, PR, SD, PD, Relapse, or Nodular PR at the End of Study
Tidsramme: Month 35
CR, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a ≥ 50% increase in greatest diameter of any previously noted lesion; 2) a ≥50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥6 months. Nodular PR was defined by the presence of residual lymphoid nodules.
Month 35
Number of Participants With Immunophenotypic CR - BM, Immunophenotypic CR - Peripheral Blood (PB), Molecular CR - BM, or Molecular CR - PB at the End of Induction Treatment
Tidsramme: Month 10
Immunophenotypic CR was defined as the absence of minimal residual disease (MRD) evaluated in participants with CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells. Molecular CR was defined as the absence of MRD evaluated in participants with CR by quantitative polymerase chain reaction (PCR) in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
Month 10
Percentage of Participants With CR, CRi, PR, SD, PD, or Relapse at the End of Study
Tidsramme: Month 35
CR, CRi, PR, SD, PD, relapse, and nodular PR as previously defined.
Month 35
Percentage of Participants With Immunophenotypic CR - BM or Immunophenotypic CR - PB at the End of Study
Tidsramme: Month 35
Immunophenotypic CR was defined as the absence of MRD evaluated in participants who achieved CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
Month 35
Percentage of Participants With Molecular CR - BM or Molecular CR - PB at the End of Study
Tidsramme: Month 35
Molecular CR was defined as the absence of MRD evaluated in participants who achieved CR by quantitative PCR in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
Month 35
Number of Participants With Disease Progression, Relapse, Death, Withdrawal Because of an Adverse Event (AE), or New CLL Treatment
Tidsramme: Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Event-free Survival (EFS) was defined as the time from the first dose of study treatment to the date of first documentation of disease progression, relapse for participants with previous CR, death due to any cause, withdrawal due to AE, or beginning new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose of study treatment.
Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
EFS
Tidsramme: Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The median time, in days, from the the date of first dose of study treatment to the date of first documentation of disease progression, relapse for participants with CR, death due to any cause, withdrawal due to AE, or new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose if study treatment. The 95% CI was determined using Kaplan-Meier methodology.
Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Number of Participants With Disease Progression or Death
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Progression-free survival (PFS) was defined as the time from the first dose of study treatment to the first documentation of disease progression or death. PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
PFS
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The median time, in days, from the date of the first dose of study treatment to the date of first documentation of disease progression or death. CR and PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment. The 95% CI was determined using Kaplan-Meier methodology.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Number of Participants With New CLL Treatment or Death
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Time to new CLL treatment (TTNT) was defined as the time from the first dose of study treatment to the date of new CLL treatment received or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Time to Next Treatment (TTNT)
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The mean time, in days, from the date of the first dose of study treatment to the date of new CLL treatment or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. Mean survival time and it's standard error (SE) were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Number of Participants Who Died
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Overall Survival (OS) was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
OS
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The mean time, in days, from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. The mean survival time and it's SE were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Number of Participants With PD or Death After a Confirmed CR, CRi, or PR
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Duration of response was defined as the time from the date of the first documented CR, CRi, or PR to the date of disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Duration of Response
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The mean time, in days, from the date of first documented CR, CRi or PR to the date disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Number of Participants With PD or Death After a Confirmed CR/CRi
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Disease-free survival was defined at the time from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
Disease-Free Survival
Tidsramme: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
The mean time, in days, from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi. In both groups, the mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Hoffmann-La Roche

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

3. november 2008

Primær fullføring (Faktiske)

14. januar 2013

Studiet fullført (Faktiske)

14. januar 2013

Datoer for studieregistrering

Først innsendt

18. august 2008

Først innsendt som oppfylte QC-kriteriene

19. august 2008

Først lagt ut (Anslag)

20. august 2008

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

15. august 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

6. juli 2017

Sist bekreftet

1. juni 2017

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ML21445
  • 2008-001612-20

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