NCT00645606

Brief Summary

RATIONALE: Classical chemotherapy does not cure advanced chronic lymphocytic leukemia (CLL) despite new drugs. Rituximab is a monoclonal antibody directed against CD20 surface antigen on B lymphocytes and leads to apoptosis of CD20 positive B lymphocytes. The highest response rate yet published in the treatment of first-line CLL has been obtained by the association of fludarabine, cyclophosphamide and rituximab (FCR). Now, the question is whether this response can be improved, as some trials showed that eradication of minimal residual disease (MRD) in CLL is associated with a longer treatment-free and overall survival. Maintenance therapy using rituximab has been recently approved as a means of prolonging remission in patients with indolent non Hodgkin's lymphoma. Maintenance therapy with rituximab could be of interest in treatment of MRD in CLL and prolonging remission and survival times. PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (\>65 years) patients who respond to induction immunochemotherapy with FCR.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
542

participants targeted

Target at P50-P75 for phase_3 leukemia

Timeline
Completed

Started Dec 2007

Longer than P75 for phase_3 leukemia

Geographic Reach
1 country

1 active site

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

Study Start

First participant enrolled

December 1, 2007

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

March 26, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 27, 2008

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2014

Completed
3.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2017

Completed
Last Updated

August 1, 2017

Status Verified

July 1, 2017

Enrollment Period

6.2 years

First QC Date

March 26, 2008

Last Update Submit

July 27, 2017

Conditions

Leukemia

Keywords

B-cell chronic lymphocytic leukemiaMaintenance in first-line treatmentElderly patients

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival

    Progression-free survival is defined as the time from randomization to the first occurrence of disease progression, relapse or death from any cause; using iwCLL criteria

    randomization until disease progression or death

Secondary Outcomes (9)

  • Event-free survival

    randomization until disease progression, death, new CLL treatment, and secondary cancer

  • Disease-free survival

    first documented CR until relapse

  • Overall survival

    randomization until death

  • Time to next treatment

    randomization until new CLL treatment

  • Overall response rate

    baseline up to approximately 66 months

  • +4 more secondary outcomes

Study Arms (2)

Observation

NO INTERVENTION

Observation every 8 weeks during 2 years

rituximab arm

EXPERIMENTAL

rituximab :500 mg/m² every 8 weeks during 2 years

Biological: Rituximab

Interventions

RituximabBIOLOGICAL

rituximab :500 mg/m² every 8 weeks during 2 years

Also known as: Mabthera
rituximab arm

Eligibility Criteria

Age65 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • B-CLL
  • Matutes score 4 or 5
  • Binet stages B or C
  • Age \> 65 years old
  • No previous treatment of CLL by chemotherapy, radiotherapy or immunotherapy, except glucocorticoids \< 1 month
  • Patient's written informed consent
  • Life expectancy \> 6 months

You may not qualify if:

  • Binet stage A
  • ECOG performance status 2 or more
  • Presence of a 17p deletion by FISH (\> 10% positive cores)
  • Clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician
  • Patients with a history of another malignancy in complete remission less than 5 years, except basal cell skin cancer or tumor treated curatively by surgery
  • Concomitant disease requiring prolonged use of corticosteroids (\> 1 month)
  • Any severe co-morbidities such as NYHA Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, severe uncontrolled myocardiopathy, uncontrolled hypertension, severe chronic obstructive pulmonary disease with hypoxemia, or uncontrolled diabetes mellitus.
  • CIRS (Cumulative Illness rating Scale) \> 6
  • Known hypersensitivity to murine proteins or to any of the study drugs or to their components
  • Transformation into an aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma) or prolymphocytic leukemia
  • Active bacterial, viral or fungal infection
  • Seropositivity HIV, hepatitis C or hepatitis B (unless clearly due to vaccination)
  • Total bilirubin, alkaline phosphatases and aminotransferases \> 2 x ULN
  • Creatinine clearance \< 60 ml/min calculated according to the formula of Cockcroft and Gault
  • Any coexisting medical or psychological condition that would preclude participation to the required study procedures
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

French Innovative leukemia Organization

Tours, 37044, France

Location

Related Publications (1)

  • Dartigeas C, Van Den Neste E, Leger J, Maisonneuve H, Berthou C, Dilhuydy MS, De Guibert S, Lepretre S, Bene MC, Nguyen-Khac F, Letestu R, Cymbalista F, Rodon P, Aurran-Schleinitz T, Vilque JP, Tournilhac O, Mahe B, Laribi K, Michallet AS, Delmer A, Feugier P, Levy V, Delepine R, Colombat P, Leblond V; CLL 2007 SA investigators; French Innovative Leukemia Organization (FILO). Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study. Lancet Haematol. 2018 Feb;5(2):e82-e94. doi: 10.1016/S2352-3026(17)30235-1. Epub 2017 Dec 20.

    PMID: 29275118DERIVED

MeSH Terms

Conditions

LeukemiaLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Caroline Dartigeas, MD

    Hématologie et Thérapie Cellulaire Hôpital Bretonneau CHU Tours FRANCE

    PRINCIPAL INVESTIGATOR

  • Eric VAN DEN NESTE, MD PhD

    Département d'hématologie Cliniques Universitaires Saint Luc BRUSSELS BELGIUM

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2008

First Posted

March 27, 2008

Study Start

December 1, 2007

Primary Completion

February 1, 2014

Study Completion

July 1, 2017

Last Updated

August 1, 2017

Record last verified: 2017-07

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)