Clinical trial NCT00738829: Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Keywords: CLL
untreated
immune therapy
dose escalation
maximum tolerated dose
maintenance therapy
Lenalidomide
Rituximab
Fludarabine
Lead sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Roche Pharma AG
First posted: 2008-08-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lenalidomide Maximum Tolerated Dose
timeFrame: Dose escalation stage
Secondary outcomes:
measure: Safety profile of Lenalidomide/Fludarabine/Rituximab treatment
timeFrame: Study Duration
measure: Safety Profile of Lenalidomide/Rituximab
timeFrame: Study duration
measure: Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment
timeFrame: Dose escalation stage
measure: Response rate for Lenalidomide/Rituximab combination therapy
timeFrame: Study Duration
measure: Response rate by 4-colour flow cytometric MRD analysis
timeFrame: Study Duration
measure: Changes in Quality of Life scores
timeFrame: Study Duration
measure: Risk factors and clonal evolution
timeFrame: Study Duration
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
state: Tirol
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Linz
country: Austria
facility: Krankenhaus d. Barmherzigen Schwestern Linz
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz GmbH
city: Linz
country: Austria
facility: Krankenhaus der Stadt Linz
city: Salzburg
country: Austria
facility: Universitaetsklinik f. Innere Medizin III
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
Study officials:
affiliation: Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg
name: Richard Greil, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Egle A, Steurer M, Melchardt T, Weiss L, Gassner FJ, Zaborsky N, Geisberger R, Catakovic K, Hartmann TN, Pleyer L, Voskova D, Thaler J, Lang A, Girschikofsky M, Petzer A, Greil R. Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study. Ann Hematol. 2018 Oct;97(10):1825-1839. doi: 10.1007/s00277-018-3380-z. Epub 2018 Jun 4.