- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00738374
A Study of MabThera (Rituximab) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia.
6 juillet 2017 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
97
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Calabria
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Catanzaro, Calabria, Italie, 88100
- Az. Osp. Pugliese; Dh Oncologico
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Cosenza, Calabria, Italie, 87100
- P.O. Annunziata; U.O. Ematologia
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Reggio Calabria, Calabria, Italie, 89100
- Ospedale Riuniti; Divisione Di Ematologia
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Campania
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Napoli, Campania, Italie, 80131
- Ospedale Cardarelli; Divisione Di Ematologia
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Emilia-Romagna
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Bologna, Emilia-Romagna, Italie, 40138
- A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
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Ferrara, Emilia-Romagna, Italie, 44100
- Arcispedale S. Anna; Sezione Di Ematologia
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Lazio
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Roma, Lazio, Italie, 00161
- Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
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Roma, Lazio, Italie, 00144
- Ospedale S. Eugenio; Divisione Di Ematologia
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Liguria
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Genova, Liguria, Italie, 16132
- Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
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Lombardia
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Milano, Lombardia, Italie, 20122
- Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
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Milano, Lombardia, Italie, 20162
- Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
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Piemonte
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Torino, Piemonte, Italie, 10126
- A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
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Torino, Piemonte, Italie, 10126
- Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
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Puglia
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Bari, Puglia, Italie, 70124
- Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
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Sicilia
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Messina, Sicilia, Italie, 98165
- Az. Osp. Papardo; Struttura Complessa Di Ematologia
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Via S. Sofia 78, Sicilia, Italie, 95123
- Ospedale Ferrarotto; Divisione Di Ematologia
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Toscana
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Firenze, Toscana, Italie, 50135
- Az. Osp. Di Careggi; Divisione Di Ematologia
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Siena, Toscana, Italie, 53100
- A.O. Universitaria Senese; Ematologia
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Veneto
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Padova, Veneto, Italie, 35128
- Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia
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Verona, Veneto, Italie, 37134
- Policlinico G. B. Rossi; Divisione Di Ematologia
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
60 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 1
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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).
8mg/m2 po on days 1-7 of courses 1-8
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Percentage of Participants With Documented CR, CRi, or PR at the End of Induction Treatment
Délai: Month 10
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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.
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Month 10
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Percentage of Participants With Documented CR, CRi, or PR at the End of Study
Délai: 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.
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Month 35
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Percentage of Participants With CR, CRi, PR, Stable Disease (SD), Progressive Disease (PD), Relapse, or Nodular PR at the End of Induction Treatment
Délai: Month 10
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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.
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Month 10
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Percentage of Participants With CR, PR, SD, PD, Relapse, or Nodular PR at the End of Study
Délai: Month 35
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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.
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Month 35
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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
Délai: Month 10
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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.
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Month 10
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Percentage of Participants With CR, CRi, PR, SD, PD, or Relapse at the End of Study
Délai: Month 35
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CR, CRi, PR, SD, PD, relapse, and nodular PR as previously defined.
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Month 35
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Percentage of Participants With Immunophenotypic CR - BM or Immunophenotypic CR - PB at the End of Study
Délai: Month 35
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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.
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Month 35
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Percentage of Participants With Molecular CR - BM or Molecular CR - PB at the End of Study
Délai: Month 35
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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.
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Month 35
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Number of Participants With Disease Progression, Relapse, Death, Withdrawal Because of an Adverse Event (AE), or New CLL Treatment
Délai: 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.
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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.
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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.
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EFS
Délai: 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.
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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.
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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.
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Number of Participants With Disease Progression or Death
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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PFS
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants With New CLL Treatment or Death
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Time to Next Treatment (TTNT)
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants Who Died
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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OS
Délai: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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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.
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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
Délai: 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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Duration of Response
Délai: 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.
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Number of Participants With PD or Death After a Confirmed CR/CRi
Délai: 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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Disease-Free Survival
Délai: 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.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
3 novembre 2008
Achèvement primaire (Réel)
14 janvier 2013
Achèvement de l'étude (Réel)
14 janvier 2013
Dates d'inscription aux études
Première soumission
18 août 2008
Première soumission répondant aux critères de contrôle qualité
19 août 2008
Première publication (Estimation)
20 août 2008
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
15 août 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
6 juillet 2017
Dernière vérification
1 juin 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Leucémie, cellule B
- Leucémie
- Leucémie lymphocytaire chronique à cellules B
- Leucémie, Lymphoïde
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antirhumatismaux
- Agents antinéoplasiques
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agents antinéoplasiques immunologiques
- Rituximab
- Chlorambucil
Autres numéros d'identification d'étude
- ML21445
- 2008-001612-20
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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