Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

Phase 1

Completed

• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Interventions: Drug: Lenalidomide; Drug: Fludarabine; Biological: Rituximab

• Registration Number: NCT00738829
• Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie

Brief Summary

The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen.

Detailed Description

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study in patients with previously untreated CD20-positive CLL. Phase I of the study will evaluate the maximal tolerated lenalidomide dose level in combination with fludarabine/rituximab chemoimmunotherapy in 10 patients. Phase II will determine efficacy using the combination in the previously defined maximal tolerated dose. Both phases will be followed by a maintenance phase evaluating the tolerability and possibility to further improve response quality.

Study Timeline

• Study First Submitted: 2008-08-20
• Study First Submitted QC: 2008-08-20
• Study First Posted: 2008-08-21
• Study Start: 2008-10
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-29
• Last Update Posted: 2013-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• B-CLL (CD23+, CD5+, CD19+, CD20+)
• Treatment indication according to NCI criteria
• Age >= 18 yrs
• No previous treatment of CLL by chemo-, radio- or immunotherapy
• Life expectancy > 6 months
• Written informed consent
• Women of non-childbearing potential or women of childbearing potential and men using effective contraception

Exclusion Criteria

• Active bacterial, viral or fungal infection
• Positivity for HIV, Hepatitis B or C
• Reduce organ functions and bone marrow dysfunction not due to CLL
• Creatinine clearance below 30 ml/min
• Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment
• Patients with a history of severe cardiac disease
• Other known co-morbidity with the potential to dominate survival
• Transformation to aggressive B-cell malignancy
• Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs
• Pregnant or breast-feeding women
• Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Rituximab	Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy
Treatment Arm	Lenalidomide	Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy
Treatment Arm	Fludarabine	Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy

Primary Outcome Measures

Name	Time	Method
Lenalidomide Maximum Tolerated Dose	Dose escalation stage

Secondary Outcome Measures

Name	Time	Method
Safety profile of Lenalidomide/Fludarabine/Rituximab treatment	Study Duration
Safety Profile of Lenalidomide/Rituximab	Study duration
Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment	Dose escalation stage
Response rate for Lenalidomide/Rituximab combination therapy	Study Duration
Response rate by 4-colour flow cytometric MRD analysis	Study Duration
Changes in Quality of Life scores	Study Duration
Risk factors and clonal evolution	Study Duration

Trial Locations

Locations (7)

Universitaetsklinik f. Innere Medizin III; 🇦🇹 Salzburg, Austria

Klinikum Wels-Grieskirchen GmbH; 🇦🇹 Wels, Austria

Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie; 🇦🇹 Innsbruck, Tirol, Austria

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria

Krankenhaus d. Barmherzigen Schwestern Linz; 🇦🇹 Linz, Austria

Krankenhaus der Stadt Linz; 🇦🇹 Linz, Austria

Krankenhaus der Elisabethinen Linz GmbH; 🇦🇹 Linz, Austria