Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

Leukemia, Lymphocytic, Chronic, B-Cell Clinical Trial

Official title:

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Concomitant Evaluation of Safety and Efficacy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00738829
• Other study ID #: CLL-5
• Secondary ID: EudraCT Nr. 2008
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 20, 2008
• Last updated: August 29, 2013
• Start date: October 2008
• Est. completion date: January 2012

Study information

• Verified date: August 2013
• Source: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyAustria: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Lenalidomide
Dose escalation stage: starting dose 2.5mg/d, dose escalation via 5/10/15/20/25 mg/d every 28 days if no dose-limiting toxicity. During maintenance stage dosing on days 1-28 for max. 6 months at maximum tolerated dose reached during dose escalation stage.
• Fludarabine
25 mg/m2 i.v. d1-3 or 40 mg/m2 po d1-3 every 28 days for 6 cycles during dose escalation stage.

Biological:
• Rituximab
Dose escalation stage: 375 mg/m2 i.v. d4 Cycle 1, 500 mg/m2 i.v. d1 Cycles 2-6. Maintenance stage: 375 mg/m2 i.v. at 2/4/6 months after end of escalation stage.

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Austria	Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie	Innsbruck	Tirol
Austria	Krankenhaus d. Barmherzigen Schwestern Linz	Linz
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Austria	Krankenhaus der Stadt Linz	Linz
Austria	Universitaetsklinik f. Innere Medizin III	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels

Sponsors (3)

Lead Sponsor	Collaborator
Arbeitsgemeinschaft medikamentoese Tumortherapie	Celgene Corporation, Roche Pharma AG

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lenalidomide Maximum Tolerated Dose		Dose escalation stage	Yes
Secondary	Safety profile of Lenalidomide/Fludarabine/Rituximab treatment		Study Duration	Yes
Secondary	Safety Profile of Lenalidomide/Rituximab		Study duration	Yes
Secondary	Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment		Dose escalation stage	No
Secondary	Response rate for Lenalidomide/Rituximab combination therapy		Study Duration	No
Secondary	Response rate by 4-colour flow cytometric MRD analysis		Study Duration	No
Secondary	Changes in Quality of Life scores		Study Duration	No
Secondary	Risk factors and clonal evolution		Study Duration	No