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Rituximab Versus Observation as Maintenance Therapy in Chronic Lymphocytic Leukemia (Chronic Lymphocytic Leukemia)

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Arbeitsgemeinschaft medikamentoese Tumortherapie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, Rituximab, Maintenance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Landesklinikum Krems, Hämato-onkologisches Service
  • AKH Linz, Department für Innere Medizin 3
  • Landeskrankenhaus Steyr, Innere Medizin, Hämatologie, Onkologie
  • Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV
  • A.ö. Bezirkskrankenhaus Hall in Tirol, Innere Medizin / Hämato - Onkologie
  • Universitätsklinik Innsbruck, Innere MEdizin IV / Hämato-Onkologie
  • A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
  • LKH Feldkirch, Interne E
  • Universitätsklinik der PMU Salzburg, Univ-Klinik für Innere Medizin
  • AKH Wien, Klinische Abteilung für Hämatologie und Hämostaseologie
  • Hanusch Krankenhaus, 3. Med. Abtlg.
  • FN Brno
  • FN Hradec Kralove
  • FN Olomouc
  • FN Kralovske Vinohrady
  • VFN Praha 2
  • F.D. Rossevelt hospital
  • Narodny onkologicky ustav
  • FNsP sv. Cyrila a Metoda
  • FNsP L.Pasteura
  • Martinska fakultna nemocnica
  • FNsP J.A. Reimana

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Rituximab

Observation

Arm Description

Treatment with Rituximab 375 mg/m² every 3 months for 24 months

Observation for 24 months

Outcomes

Primary Outcome Measures

progression free survival
Clinical PFS is defined as the period from randomization until disease progression according to the NCI criteria or death due to the underlying disease.

Secondary Outcome Measures

MRD (minimal residual disease) progression free survival
Minimal residual disease progression-free survival is defined as the period from randomization until increase of MRD levels in peripheral blood above 10-3 or, if above 10-3 before, increase of one common logarithm.
conversion rate to MRD negative
median MRD levels
conversation rate to CR
effect of MRD levels on clinical PFS and OS
event free survival
time to next treatment
overall survival
Safety of Rituximab maintenance treatment in patients with CLL
All grades of infections and G3/4 other clinical adverse events will be documented using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
benefit according to cytogenetic risk group (trisomy 12, del 11q, del 17p and del 13q), IgVH mutation status, ZAP 70 and CD38 expression

Full Information

First Posted
May 3, 2010
Last Updated
January 6, 2020
Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Roche Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT01118234
Brief Title
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 2009 (Actual)
Primary Completion Date
February 2018 (Actual)
Study Completion Date
July 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Roche Pharma AG

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
CLL, Rituximab, Maintenance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
256 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Treatment with Rituximab 375 mg/m² every 3 months for 24 months
Arm Title
Observation
Arm Type
No Intervention
Arm Description
Observation for 24 months
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab (MabThera, F. Hoffmann-La Roche Ltd., Basel, Switzerland) 375 mg/m² every 3 months for 24 months (8 infusions) or observation
Primary Outcome Measure Information:
Title
progression free survival
Description
Clinical PFS is defined as the period from randomization until disease progression according to the NCI criteria or death due to the underlying disease.
Time Frame
48 months
Secondary Outcome Measure Information:
Title
MRD (minimal residual disease) progression free survival
Description
Minimal residual disease progression-free survival is defined as the period from randomization until increase of MRD levels in peripheral blood above 10-3 or, if above 10-3 before, increase of one common logarithm.
Time Frame
48 months
Title
conversion rate to MRD negative
Time Frame
48 months
Title
median MRD levels
Time Frame
48 months
Title
conversation rate to CR
Time Frame
48 months
Title
effect of MRD levels on clinical PFS and OS
Time Frame
48 months
Title
event free survival
Time Frame
48 months
Title
time to next treatment
Time Frame
48 months
Title
overall survival
Time Frame
48 months
Title
Safety of Rituximab maintenance treatment in patients with CLL
Description
All grades of infections and G3/4 other clinical adverse events will be documented using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
Time Frame
48 months
Title
benefit according to cytogenetic risk group (trisomy 12, del 11q, del 17p and del 13q), IgVH mutation status, ZAP 70 and CD38 expression
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Greil, Prof. Dr.
Organizational Affiliation
Arbeitsgemeinschaft medikamentoese Tumortherapie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Landesklinikum Krems, Hämato-onkologisches Service
City
Krems
State/Province
Niederösterreich
ZIP/Postal Code
3500
Country
Austria
Facility Name
AKH Linz, Department für Innere Medizin 3
City
Linz
State/Province
Oberösterreich
ZIP/Postal Code
4021
Country
Austria
Facility Name
Landeskrankenhaus Steyr, Innere Medizin, Hämatologie, Onkologie
City
Steyr
State/Province
Oberösterreich
ZIP/Postal Code
4400
Country
Austria
Facility Name
Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV
City
Wels
State/Province
Oberösterreich
ZIP/Postal Code
4600
Country
Austria
Facility Name
A.ö. Bezirkskrankenhaus Hall in Tirol, Innere Medizin / Hämato - Onkologie
City
Hall In Tirol
State/Province
Tirol
ZIP/Postal Code
6060
Country
Austria
Facility Name
Universitätsklinik Innsbruck, Innere MEdizin IV / Hämato-Onkologie
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
6020
Country
Austria
Facility Name
A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
City
Kufstein
State/Province
Tirol
ZIP/Postal Code
6330
Country
Austria
Facility Name
LKH Feldkirch, Interne E
City
Feldkirch
State/Province
Vorarlberg
ZIP/Postal Code
6807
Country
Austria
Facility Name
Universitätsklinik der PMU Salzburg, Univ-Klinik für Innere Medizin
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
AKH Wien, Klinische Abteilung für Hämatologie und Hämostaseologie
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Hanusch Krankenhaus, 3. Med. Abtlg.
City
Wien
ZIP/Postal Code
1140
Country
Austria
Facility Name
FN Brno
City
Brno
ZIP/Postal Code
62588
Country
Czechia
Facility Name
FN Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
FN Olomouc
City
Olomouc
Country
Czechia
Facility Name
FN Kralovske Vinohrady
City
Praha
ZIP/Postal Code
10034
Country
Czechia
Facility Name
VFN Praha 2
City
Praha
ZIP/Postal Code
12808
Country
Czechia
Facility Name
F.D. Rossevelt hospital
City
Banská Bystrica
ZIP/Postal Code
97517
Country
Slovakia
Facility Name
Narodny onkologicky ustav
City
Bratislava
ZIP/Postal Code
83310
Country
Slovakia
Facility Name
FNsP sv. Cyrila a Metoda
City
Bratislava
ZIP/Postal Code
85107
Country
Slovakia
Facility Name
FNsP L.Pasteura
City
Kosice
ZIP/Postal Code
04190
Country
Slovakia
Facility Name
Martinska fakultna nemocnica
City
Martin
ZIP/Postal Code
03659
Country
Slovakia
Facility Name
FNsP J.A. Reimana
City
Presov
ZIP/Postal Code
08181
Country
Slovakia

12. IPD Sharing Statement

Citations:
PubMed Identifier
27374465
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.
Results Reference
derived

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Rituximab Versus Observation as Maintenance Therapy in Chronic Lymphocytic Leukemia (Chronic Lymphocytic Leukemia)

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