Intensified Rituimab Prephase Before FCR in Untreated B-CLL

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2011 by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Sponsor:
Collaborators:
GCFLLC MW intergroup
Roche Pharma AG
Information provided by:
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier:
NCT01370772
First received: May 23, 2011
Last updated: June 9, 2011
Last verified: June 2011
  Purpose

Phase II, multicenter, randomized trial, exploring intensified Rituximab prephase monotherapy before standard Fludarabine-Cyclophosphamide-Rituximab FC-R regimen in previously untreated symptomatic B-cell chronic lymphocytic leukemia CLL.

A Study from the Goelams GCFLLCMW intergroup


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia CLL
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Multicentric, Randomized Trial, Exploring Intensified Rituximab Prephase Monotherapy Before Standard Fludarabine-Cyclophosphamide-Rituximab Regimen in Previously Untreated Symptomatic B-cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:

Primary Outcome Measures:
  • complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab


Secondary Outcome Measures:
  • To determine and compare the progression free survival PFS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Treatment evaluation

  • To evaluate FcyRs polymorphisms influence on clinical response [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    R Dense arm treatment evaluation

  • To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To evaluate the safety profile of higher doses of rituximab [ Time Frame: 41 ] [ Designated as safety issue: Yes ]
    5 months treatment and 36 months follow up

  • To determine the event-free survival EFS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To determine and compare the disease-free survival DFS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To determine the overall survival OS [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To determine the time to next treatment TTNT [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 140
Study Start Date: May 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard R-FC arm
FCR courses
Drug: Rituximab
  • Cycle 1 Rituximab : 375 mg/m² i.v on day 1
  • Cycle 2-6 Rituximab:500 mg/m² i.v on day 1, repeated every 28 days
Other Name: R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Name: C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Name: F
Experimental: DenseR-FC arm
1 prephase R Dense course 6 FCR courses
Drug: Rituximab
  • Prephase: Rituximab:500 mg on day 0, 2000 mg on days 1, 8, and D15
  • Cycle 1-6 cycle 1 beginning at D22: Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
Other Name: R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Name: C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Name: F

Detailed Description:

Young fit medically B Cell untreated patients Comparison between FCR treatment = 6 FCR cycles and a the addition of a prephase with R Dense treatment before the 6 FCR cycles.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patient information and written informed consent
  • 18 years < Age < 66 ans
  • confirmed B-CLL Matutes score 4 or 5
  • Binet stage C or Binet stage A and B with active disease could be considered for inclusion. For stage A with active disease an agreement of investigator coordinator is required.
  • no prior treatment except steroids for less than 1 month (detail corticoid)
  • No 17p deletion as assessed by FISH < 10 % positive nuclei
  • Performance status ECOG < 2
  • CIRS Cumulative Illness Rating Scale < 6

Exclusion criteria:

  • Binet stage A without active disease according to IWCLL 2008 criteria
  • Know HIV seropositivity
  • Hepatitis B or C seropositivity unless clearly due to vaccination
  • Life expectancy < 6 months
  • Clinically significant auto-immune anemia
  • Active second malignancy currently requiring treatment (except basal cell carcinoma in situ endometrial carcinoma and incidental prostate carcinoma) and/or less than 5 years CR after breast cancer
  • Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension
  • Concomitant disease requiring prolonged use of corticosteroids > 1 month
  • Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs According to the SmPC or investigator practice
  • Contraindication to use of Rituximab
  • Transformation to aggressive B-cell malignancy e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia
  • Active bacterial, viral or fungal infection
  • Abnormal renal function with creatinine clearance < 60 ml/min calculated according to the Cockcroft and Gault formula
  • Total bilirubin, gamma glutamyltransferase or transaminase levels > 2.5 ULN.
  • Any coexisting medical or psychological condition that would preclude participation in the required study procedures
  • Patient with mental deficiency preventing proper understanding of the requirements of treatment.
  • Pregnant or breastfeeding women.
  • Adult under law-control
  • Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.
  • No afiliate to social security
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370772

Contacts
Contact: Guillaume CARTRON, MD PD + 33 4 67 33 83 62 g-cartron@chu-montpellier.fr
Contact: Stephane LEPRETRE, MD +33 2 32 08 22 19 slepretre@rouen.fnclcc.fr

Locations
France
Stephane LEPRETRE Recruiting
Rouen, CLCC Henri Becquerel, France, 76038
Contact: Sandrine VAUDAUX, biology CRA    +33 2 32 08 24 96    svaudaux@rouen.fnclcc.fr   
Guillaume CARTRON Recruiting
Montpellier, Regional university Hospital, France, 34295
Contact: Valerie ROUILLE, CRA manager    +33 4 67 33 83 66    vrouille@reshom-rc.fr   
Contact: Roselyne DELEPINE, PV CRA    +33 2 47 47 37 98    r.delepine@chu-tours.fr   
Sponsors and Collaborators
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
GCFLLC MW intergroup
Roche Pharma AG
Investigators
Principal Investigator: Guillaume CARTRON, MD PD Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Principal Investigator: Stephane LEPRETRE, MD GCFLLC MW intergroup
  More Information

Additional Information:
No publications provided

Responsible Party: CLL2010FMP Fit Medically patient, GOELAMS
ClinicalTrials.gov Identifier: NCT01370772     History of Changes
Other Study ID Numbers: CLL 2010 FMP
Study First Received: May 23, 2011
Last Updated: June 9, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:
B CLL
Fist line treatment

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Rituximab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on September 16, 2014