Clinical trial NCT00545714: A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL)
Official title: Multicentre, Non-Randomised, Open-Label Phase II Study to Evaluate the Efficacy and Safety of Induction Treatment With Rituximab, Fludarabine, Cyclophosphamide, Followed by Rituximab Maintenance Therapy (R-Fc-Rm) in the First Line Treatment of Chronic Lymphocytic Leukaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-10-17
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm study will assess the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with CLL.


Eligibility criteria: Inclusion Criteria:

* CLL according to World Health Organization diagnostic criteria
* Active disease
* No previous treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

* Transformation to aggressive B-cell malignancy (prolymphocytic leukemia, large-cell lymphoma, Hodgkin's lymphoma)
* Other malignancies except for localized skin cancer
* Continuous systemic corticosteroid treatment
* Known infection with hepatitis B or C

Primary outcomes:
measure: Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
timeFrame: Month 9
Secondary outcomes:
measure: Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
timeFrame: Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36
measure: Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
timeFrame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36
measure: Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)
timeFrame: Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)
measure: Percentage of Participants Who Died
timeFrame: Baseline up to death due to any cause (up to 92 months)
measure: Overall Survival (OS)
timeFrame: Baseline up to death due to any cause (up to 92 months)
measure: Percentage of Participants With PD or Death
timeFrame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
measure: Treatment-Free Survival (TFS)
timeFrame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
measure: Duration of Response (DOR)
timeFrame: From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)
measure: Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
timeFrame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
measure: Percentage of Participants With Genetic Abnormalities
timeFrame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)
measure: Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
timeFrame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
measure: Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
timeFrame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital De Txagorritxu; Servicio de Hematologia
state: Alava
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar; Servicio de Hematologia
state: Cadiz
city: Jerez de La Frontera
country: Spain
facility: Hospital de Jerez de la Frontera; Servicio de Hematologia
state: Cadiz
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
state: Cantabria
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
state: LA Coruña
city: Alcorcon
country: Spain
facility: Fundacion Hospital de Alcorcon; Servicio de Hematologia
state: Madrid
city: Mostoles
country: Spain
facility: Hosital Universitario de Mostoles;Servicio de Hematologia
state: Madrid
city: Gandia
country: Spain
facility: Hospital Francesc de Borja; Servicio de Hematologia
state: Valencia
city: Sagunto
country: Spain
facility: Hospital de Sagunto; Servicio de Hematologia
state: Valencia
city: Bilbao
country: Spain
facility: Hospital de Basurto; Servicio de Hematologia
state: Vizcaya
city: Badajoz
country: Spain
facility: Hospital Universitario Infanta Cristina; Servicio de Hematologia
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals; Servicio de Hematologia
city: Caceres
country: Spain
facility: Hospital San Pedro De Alcantara; Servicio de Hematologia
city: Castellon
country: Spain
facility: Hospital General de Castellon; Servicio de Hematologia
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Hematología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Hematología
city: Madrid
country: Spain
facility: Hospital Univ. 12 de Octubre; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario la Paz; Servicio de Hematologia
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Principe de Asturias; Servicio de Hematología
city: Madrid
country: Spain
facility: Hospital Universitario de Getafe; Servico de Hematologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Hematologia
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia; Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset; Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Hematologia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Hematologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Garcia-Marco JA, Jimenez JL, Recasens V, Zarzoso MF, Gonzalez-Barca E, De Marcos NS, Ramirez MJ, Parraga FJP, Yanez L, De La Serna Torroba J, Malo MDG, Ariznavarreta GD, Persona EP, Guinaldo MAR, De Paz Arias R, Llanos EB, Jarque I, Valle MDCF, Tatay AC, De Oteyza JP, Martin EMD, Fernandez IP, Martinez RM, Costa MAA, Champ D, Suarez JG, Diaz MG, Ferrer S, Carbonell F, Garcia-Vela JA; GELLC Study Group. High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance. Haematologica. 2019 Nov;104(11):2249-2257. doi: 10.3324/haematol.2018.204891. Epub 2019 Mar 19.