NCT00738829

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2008

Typical duration for phase_1

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 20, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 21, 2008

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2008

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
Last Updated

August 30, 2013

Status Verified

August 1, 2013

Enrollment Period

3.3 years

First QC Date

August 20, 2008

Last Update Submit

August 29, 2013

Conditions

Keywords

CLLuntreatedimmune therapydose escalationmaximum tolerated dosemaintenance therapyLenalidomideRituximabFludarabine

Outcome Measures

Primary Outcomes (1)

  • Lenalidomide Maximum Tolerated Dose

    Dose escalation stage

Secondary Outcomes (7)

  • 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

  • +2 more secondary outcomes

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Drug: LenalidomideDrug: FludarabineBiological: Rituximab

Interventions

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.

Also known as: Revlimid
Treatment Arm

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

Also known as: Fludarabine phosphate
Treatment Arm
RituximabBIOLOGICAL

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.

Also known as: MabThera
Treatment Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie

Innsbruck, Tyrol, A-6020, Austria

Location

Landeskrankenhaus Feldkirch

Feldkirch, A-6806, Austria

Location

Krankenhaus d. Barmherzigen Schwestern Linz

Linz, A-4010, Austria

Location

Krankenhaus der Elisabethinen Linz GmbH

Linz, A-4010, Austria

Location

Krankenhaus der Stadt Linz

Linz, A-4020, Austria

Location

Universitaetsklinik f. Innere Medizin III

Salzburg, A-5020, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Wels, A-4600, Austria

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomidefludarabinefludarabine phosphateRituximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Richard Greil, Prof. Dr.

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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 20, 2008

First Posted

August 21, 2008

Study Start

October 1, 2008

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

August 30, 2013

Record last verified: 2013-08

Locations