Intensified Rituimab Prephase Before FCR in Untreated B-CLL

NCT01370772 | Completed Phase 2 DMC

• 1 other identifier: CLL 2010 FMP
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

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

Conditions

B-cell Chronic Lymphocytic Leukemia CLL

Keywords

B CLL; Fist line treatment

Outcome Measures

Primary Outcomes (1)

• complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease

  CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab

  9 months

Secondary Outcomes (9)

• To determine and compare the progression free survival PFS

  3 years

• evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC

  9 months

• To evaluate FcyRs polymorphisms influence on clinical response

  9 months

• To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers.

  12 months

• To evaluate the safety profile of higher doses of rituximab

  41

Study Arms (2)

Standard R-FC arm

ACTIVE COMPARATOR

Standard R-FC arm 6 cycles every 28 days * Cycle 1: * Rituximab : 375 mg/m² i.v on day 1 * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count \> 25\* G/L : rituximab in two equal doses at D1, D2 * Cycle 2-6: * Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

DenseR-FC arm

EXPERIMENTAL

DenseR-FC arm =1 prephase R Dense course +6 R-FC courses * Prephase: \- Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count \> 25\* G/L : rituximab 250 mg D-1, D0 prephase * Cycle 1-6 (cycle 1 beginning at D22): * Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Rituximab DRUG

* 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

Also known as: R

Standard R-FC arm

Cyclophosphamide DRUG

•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days

Also known as: C

DenseR-FC arm; Standard R-FC arm

Fludarabine DRUG

FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days

Also known as: F

DenseR-FC arm; Standard R-FC arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient information and written informed consent
• years \< Age \< 66 ans
• confirmed B-CLL Matutes score 4 or 5
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Roche Pharma AG: collaborator

Study Sites (2)

Stephane LEPRETRE

Rouen, CLCC Henri Becquerel, 76038, France

Location

Guillaume CARTRON

Montpellier, Regional University Hospital, 34295, France

Location

Related Publications (3)

• 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.

  PMID: 36325355 DERIVED

• 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.

  PMID: 28126961 DERIVED

• 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.

  PMID: 27783363 DERIVED

Related Links

• FILO Website

MeSH Terms

Interventions

Rituximab; Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Guillaume CARTRON, MD PD

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

• Stephane LEPRETRE, MD

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2011
• First Posted: June 10, 2011
• Study Start: May 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: March 1, 2016
• Last Updated: March 16, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)