Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

NCT ID: NCT00738829

Last Updated: 2013-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-01-31

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

CLL; untreated; immune therapy; dose escalation; maximum tolerated dose; maintenance therapy; Lenalidomide; Rituximab; Fludarabine

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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

Intervention Type: DRUG

25 mg/m2 i.v. d1-3 or 40 mg/m2 po d1-3 every 28 days for 6 cycles during dose escalation stage.

Rituximab

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Revlimid; Fludarabine phosphate; MabThera

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Arbeitsgemeinschaft medikamentoese Tumortherapie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Greil, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg

Locations

Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie

Innsbruck, Tyrol, Austria

Landeskrankenhaus Feldkirch

Feldkirch, , 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, , Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 29862437 (View on PubMed)

Other Identifiers

EudraCT Nr. 2008-001430-27

Identifier Type: -

Identifier Source: secondary_id

ML21718

Identifier Type: -

Identifier Source: secondary_id

CLL-5

Identifier Type: -

Identifier Source: org_study_id