Clinical trial NCT01370772: Intensified Rituimab Prephase Before FCR in Untreated B-CLL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Chronic Lymphocytic Leukemia CLL
Keywords: B CLL
Fist line treatment
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2011-06-10
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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 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

Primary outcomes:
measure: complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
timeFrame: 9 months
Secondary outcomes:
measure: To determine and compare the progression free survival PFS
timeFrame: 3 years
measure: evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC
timeFrame: 9 months
measure: To evaluate FcyRs polymorphisms influence on clinical response
timeFrame: 9 months
measure: To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers.
timeFrame: 12 months
measure: To evaluate the safety profile of higher doses of rituximab
timeFrame: 41
measure: To determine the event-free survival EFS
timeFrame: 3 years
measure: To determine and compare the disease-free survival DFS
timeFrame: 3 years
measure: To determine the overall survival OS
timeFrame: 3 years
measure: To determine the time to next treatment TTNT
timeFrame: 3 years
Other outcomes:
Locations:
city: Rouen
country: France
facility: Stephane LEPRETRE
state: CLCC Henri Becquerel
city: Montpellier
country: France
facility: Guillaume CARTRON
state: Regional university Hospital
Study officials:
affiliation: French Innovative Leukemia Organisation
name: Guillaume CARTRON, MD PD
role: PRINCIPAL_INVESTIGATOR
affiliation: French Innovative Leukemia Organisation
name: Stephane LEPRETRE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duroux-Richard I, Gagez AL, Alaterre E, Letestu R, Khalifa O, Jorgensen C, Lepretre S, Tchernonog E, Moreaux J, Cartron G, Apparailly F. miRNA profile at diagnosis predicts treatment outcome in patients with B-chronic lymphocytic leukemia: A FILO study. Front Immunol. 2022 Oct 17;13:983771. doi: 10.3389/fimmu.2022.983771. eCollection 2022.
citation: Gagez AL, Duroux-Richard I, Lepretre S, Orsini-Piocelle F, Letestu R, De Guibert S, Tuaillon E, Leblond V, Khalifa O, Gouilleux-Gruart V, Banos A, Tournilhac O, Dupuis J, Jorgensen C, Cartron G, Apparailly F. miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study. Haematologica. 2017 Apr;102(4):746-754. doi: 10.3324/haematol.2016.153189. Epub 2017 Jan 25.
citation: Tout M, Gagez AL, Lepretre S, Gouilleux-Gruart V, Azzopardi N, Delmer A, Mercier M, Ysebaert L, Laribi K, Gonzalez H, Paintaud G, Cartron G, Ternant D. Influence of FCGR3A-158V/F Genotype and Baseline CD20 Antigen Count on Target-Mediated Elimination of Rituximab in Patients with Chronic Lymphocytic Leukemia: A Study of FILO Group. Clin Pharmacokinet. 2017 Jun;56(6):635-647. doi: 10.1007/s40262-016-0470-8.