Clinical trial NCT01118234: Rituximab Versus Observation as Maintenance Therapy in Chronic Lymphocytic Leukemia (Chronic Lymphocytic Leukemia)
Official title: International, Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation Alone in Patients With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: CLL
Rituximab
Maintenance
Lead sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2010-05-06
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the ability of Rituximab maintenance therapy to prolong progression free survival in patients with chronic lymphocytic leukemia, who responded to a Rituximab induction therapy.


Eligibility criteria: Inclusion Criteria:

* B-CLL
* Age \>18
* ECOG performance status 0-2
* Previous Rituximab containing induction treatment of the CLL in 1st or 2nd line
* Patient must be in complete remission or partial remission after an induction treatment containing rituximab
* ANC (absolute neutrophil count) \> 1,0 x 10e9 /L
* Life expectancy \> 6 months
* Patient´s written informed consent
* Patient using a reliable means of contraception for the duration of the treatment including 2 months thereafter

Exclusion Criteria:

* Active uncontrolled bacterial, viral or fungal infection
* Significantly reduced organ functions and bone marrow dysfunction not due to CLL
* creatinine clearance of below 30mL/min
* Patients with a history of other malignancies within 2 years prior to study entry
* Patients with a history of severe cardiac disease
* Other known comorbidity with the potential to dominate survival
* Transformation to aggressive B-cell malignancy
* Hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the applied drugs
* Medical condition requiring prolonged (\> 1 month) use of oral corticosteroids
* Pregnant or breast feeding women
* Any coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Primary outcomes:
measure: progression free survival
timeFrame: 48 months
Secondary outcomes:
measure: MRD (minimal residual disease) progression free survival
timeFrame: 48 months
measure: conversion rate to MRD negative
timeFrame: 48 months
measure: median MRD levels
timeFrame: 48 months
measure: conversation rate to CR
timeFrame: 48 months
measure: effect of MRD levels on clinical PFS and OS
timeFrame: 48 months
measure: event free survival
timeFrame: 48 months
measure: time to next treatment
timeFrame: 48 months
measure: overall survival
timeFrame: 48 months
measure: Safety of Rituximab maintenance treatment in patients with CLL
timeFrame: 48 months
measure: benefit according to cytogenetic risk group (trisomy 12, del 11q, del 17p and del 13q), IgVH mutation status, ZAP 70 and CD38 expression
timeFrame: 48 months
Other outcomes:
Locations:
city: Krems
country: Austria
facility: Landesklinikum Krems, Hämato-onkologisches Service
state: Niederösterreich
city: Linz
country: Austria
facility: AKH Linz, Department für Innere Medizin 3
state: Oberösterreich
city: Steyr
country: Austria
facility: Landeskrankenhaus Steyr, Innere Medizin, Hämatologie, Onkologie
state: Oberösterreich
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV
state: Oberösterreich
city: Hall In Tirol
country: Austria
facility: A.ö. Bezirkskrankenhaus Hall in Tirol, Innere Medizin / Hämato - Onkologie
state: Tirol
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck, Innere MEdizin IV / Hämato-Onkologie
state: Tirol
city: Kufstein
country: Austria
facility: A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
state: Tirol
city: Feldkirch
country: Austria
facility: LKH Feldkirch, Interne E
state: Vorarlberg
city: Salzburg
country: Austria
facility: Universitätsklinik der PMU Salzburg, Univ-Klinik für Innere Medizin
city: Wien
country: Austria
facility: AKH Wien, Klinische Abteilung für Hämatologie und Hämostaseologie
city: Wien
country: Austria
facility: Hanusch Krankenhaus, 3. Med. Abtlg.
city: Brno
country: Czechia
facility: FN Brno
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
city: Olomouc
country: Czechia
facility: FN Olomouc
city: Praha
country: Czechia
facility: FN Kralovske Vinohrady
city: Praha
country: Czechia
facility: VFN Praha 2
city: Banská Bystrica
country: Slovakia
facility: F.D. Rossevelt hospital
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Bratislava
country: Slovakia
facility: FNsP sv. Cyrila a Metoda
city: Kosice
country: Slovakia
facility: FNsP L.Pasteura
city: Martin
country: Slovakia
facility: Martinska fakultna nemocnica
city: Presov
country: Slovakia
facility: FNsP J.A. Reimana
Study officials:
affiliation: Arbeitsgemeinschaft medikamentoese Tumortherapie
name: Richard Greil, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Greil R, Obrtlikova P, Smolej L, Kozak T, Steurer M, Andel J, Burgstaller S, Mikuskova E, Gercheva L, Nosslinger T, Papajik T, Ladicka M, Girschikofsky M, Hrubisko M, Jager U, Fridrik M, Pecherstorfer M, Kralikova E, Burcoveanu C, Spasov E, Petzer A, Mihaylov G, Raynov J, Oexle H, Zabernigg A, Flochova E, Palasthy S, Stehlikova O, Doubek M, Altenhofer P, Pleyer L, Melchardt T, Klingler A, Mayer J, Egle A. Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial. Lancet Haematol. 2016 Jul;3(7):e317-29. doi: 10.1016/S2352-3026(16)30045-X. Epub 2016 Jun 16.