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Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell

Status
Completed
Phase
Phase 1
Locations
Austria
Study Type
Interventional
Intervention
Lenalidomide
Fludarabine
Rituximab
Sponsored by
Arbeitsgemeinschaft medikamentoese Tumortherapie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring CLL, untreated, immune therapy, dose escalation, maximum tolerated dose, maintenance therapy, Lenalidomide, Rituximab, Fludarabine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
  • Landeskrankenhaus Feldkirch
  • Krankenhaus d. Barmherzigen Schwestern Linz
  • Krankenhaus der Elisabethinen Linz GmbH
  • Krankenhaus der Stadt Linz
  • Universitaetsklinik f. Innere Medizin III
  • Klinikum Wels-Grieskirchen GmbH

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

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

Outcomes

Primary Outcome Measures

Lenalidomide Maximum Tolerated Dose

Secondary Outcome Measures

Safety profile of Lenalidomide/Fludarabine/Rituximab treatment
Safety Profile of Lenalidomide/Rituximab
Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment
Response rate for Lenalidomide/Rituximab combination therapy
Response rate by 4-colour flow cytometric MRD analysis
Changes in Quality of Life scores
Risk factors and clonal evolution

Full Information

First Posted
August 20, 2008
Last Updated
August 29, 2013
Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Celgene Corporation, Roche Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT00738829
Brief Title
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

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arbeitsgemeinschaft medikamentoese Tumortherapie
Collaborators
Celgene Corporation, Roche Pharma AG

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell
Keywords
CLL, untreated, immune therapy, dose escalation, maximum tolerated dose, maintenance therapy, Lenalidomide, Rituximab, Fludarabine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
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
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabine phosphate
Intervention Description
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
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera
Intervention Description
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.
Primary Outcome Measure Information:
Title
Lenalidomide Maximum Tolerated Dose
Time Frame
Dose escalation stage
Secondary Outcome Measure Information:
Title
Safety profile of Lenalidomide/Fludarabine/Rituximab treatment
Time Frame
Study Duration
Title
Safety Profile of Lenalidomide/Rituximab
Time Frame
Study duration
Title
Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment
Time Frame
Dose escalation stage
Title
Response rate for Lenalidomide/Rituximab combination therapy
Time Frame
Study Duration
Title
Response rate by 4-colour flow cytometric MRD analysis
Time Frame
Study Duration
Title
Changes in Quality of Life scores
Time Frame
Study Duration
Title
Risk factors and clonal evolution
Time Frame
Study Duration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Greil, Prof. Dr.
Organizational Affiliation
Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
City
Innsbruck
State/Province
Tirol
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Landeskrankenhaus Feldkirch
City
Feldkirch
ZIP/Postal Code
A-6806
Country
Austria
Facility Name
Krankenhaus d. Barmherzigen Schwestern Linz
City
Linz
ZIP/Postal Code
A-4010
Country
Austria
Facility Name
Krankenhaus der Elisabethinen Linz GmbH
City
Linz
ZIP/Postal Code
A-4010
Country
Austria
Facility Name
Krankenhaus der Stadt Linz
City
Linz
ZIP/Postal Code
A-4020
Country
Austria
Facility Name
Universitaetsklinik f. Innere Medizin III
City
Salzburg
ZIP/Postal Code
A-5020
Country
Austria
Facility Name
Klinikum Wels-Grieskirchen GmbH
City
Wels
ZIP/Postal Code
A-4600
Country
Austria

12. IPD Sharing Statement

Citations:
PubMed Identifier
29862437
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. Erratum In: Ann Hematol. 2018 Jun 23;:
Results Reference
derived

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Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

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