A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL)
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
2 other identifiers
interventional
86
1 country
33
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2007
Longer than P75 for phase_2
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 16, 2007
CompletedFirst Posted
Study publicly available on registry
October 17, 2007
CompletedStudy Start
First participant enrolled
November 21, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 20, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2016
CompletedResults Posted
Study results publicly available
January 16, 2019
CompletedJanuary 16, 2019
July 1, 2018
8.5 years
October 16, 2007
May 16, 2017
July 27, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (\<) 4000 per cubic millimeter (mm\^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (\>) 1500/mm\^3, platelets (Plt) \>100,000/mm\^3, hemoglobin (Hb) \>11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Month 9
Secondary Outcomes (13)
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
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
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
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
Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)
Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)
Percentage of Participants Who Died
Baseline up to death due to any cause (up to 92 months)
Overall Survival (OS)
Baseline up to death due to any cause (up to 92 months)
- +8 more secondary outcomes
Study Arms (1)
Rituximab + Fludarabine + Cyclophosphamide
EXPERIMENTALParticipants will receive 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter \[mg/m\^2\] as intravenous \[IV\] infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m\^2 on Days 1-3) and cyclophosphamide (250 mg/m\^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
Interventions
Cyclophosphamide 250 mg/m\^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles.
Fludarabine 25 mg/m\^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles.
Rituximab 375 mg/m\^2 as IV infusion will be administered on Day 0 of Cycle 1; 500 mg/m\^2 as IV infusion will be administered on Day 1 of Cycle 2-6; and 375 mg/m\^2 as IV infusion every 2 months from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Hospital De Txagorritxu; Servicio de Hematologia
Vitoria-Gasteiz, Alava, 01009, Spain
Hospital Universitario Puerta del Mar; Servicio de Hematologia
Cadiz, Cadiz, 11009, Spain
Hospital de Jerez de la Frontera; Servicio de Hematologia
Jerez de la Frontera, Cadiz, 11407, Spain
Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
Santander, Cantabria, 39008, Spain
Hospital General de Castellon; Servicio de Hematologia
Castellon, Castellon, 12004, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
A Coruña, LA Coruña, 15006, Spain
Fundacion Hospital de Alcorcon; Servicio de Hematologia
Alcorcón, Madrid, 28922, Spain
Hosital Universitario de Mostoles;Servicio de Hematologia
Móstoles, Madrid, 28935, Spain
Hospital Francesc de Borja; Servicio de Hematologia
Gandia, Valencia, 46702, Spain
Hospital de Sagunto; Servicio de Hematologia
Sagunto, Valencia, 46520, Spain
Hospital de Basurto; Servicio de Hematologia
Bilbao, Vizcaya, 48013, Spain
Hospital Universitario Infanta Cristina; Servicio de Hematologia
Badajoz, 06080, Spain
Hospital Duran i Reynals; Servicio de Hematologia
Barcelona, 08907, Spain
Hospital San Pedro De Alcantara; Servicio de Hematologia
Cáceres, 10003, Spain
Hospital Universitario Virgen de las Nieves; Servicio de Hematologia
Granada, 18014, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Hematología
Madrid, 28007, Spain
Hospital Ramon y Cajal; Servicio de Hematologia
Madrid, 28034, Spain
Hospital Universitario Clínico San Carlos; Servicio de Hematología
Madrid, 28040, Spain
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Madrid, 28041, Spain
Hospital Universitario la Paz; Servicio de Hematologia
Madrid, 28046, Spain
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
Madrid, 28050, Spain
Hospital Universitario Puerta de Hierro; Servicio de Hematologia
Madrid, 28222, Spain
Hospital Universitario Principe de Asturias; Servicio de Hematología
Madrid, 28805, Spain
Hospital Universitario de Getafe; Servico de Hematologia
Madrid, 28905, Spain
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Hematologia
Málaga, 29010, Spain
Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
Murcia, 30008, Spain
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Salamanca, 37007, Spain
Hospital General Universitario de Valencia; Servicio de Hematologia
Valencia, 46014, Spain
Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia
Valencia, 46015, Spain
Hospital Universitario Dr. Peset; Servicio de Hematologia
Valencia, 46017, Spain
Hospital Universitario la Fe; Servicio de Hematologia
Valencia, 46026, Spain
Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia
Zaragoza, 50009, Spain
Hospital Universitario Miguel Servet; Servicio Hematologia
Zaragoza, 50009, Spain
Related Publications (1)
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.
PMID: 30890600DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 16, 2007
First Posted
October 17, 2007
Study Start
November 21, 2007
Primary Completion
May 20, 2016
Study Completion
May 20, 2016
Last Updated
January 16, 2019
Results First Posted
January 16, 2019
Record last verified: 2018-07