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

Study Overview
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Brief Summary
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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.

Official Title
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International, Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation Alone in Patients With Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Treatment with Rituximab 375 mg/m² every 3 months for 24 months | Drug: Rituximab<br>* Rituximab (MabThera, F. Hoffmann-La Roche Ltd., Basel, Switzerland) 375 mg/m² every 3 months for 24 months (8 infusions) or observation<br>|
| No Intervention: Observation<br>Observation for 24 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 months | 
| conversion rate to MRD negative |  | 48 months | 
| median MRD levels |  | 48 months | 
| conversation rate to CR |  | 48 months | 
| effect of MRD levels on clinical PFS and OS |  | 48 months | 
| event free survival |  | 48 months | 
| time to next treatment |  | 48 months | 
| overall survival |  | 48 months | 
| 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 | 48 months | 
| benefit according to cytogenetic risk group (trisomy 12, del 11q, del 17p and del 13q), IgVH mutation status, ZAP 70 and CD38 expression |  | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Rituximab, Maintenance