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B-cell Chronic Lymphocytic Leukemia CLLPhase 2NCT01370772

Intensified Rituimab Prephase Before FCR in Untreated B-CLL

A Phase 2 study testing Rituximab, Cyclophosphamide and Fludarabine in people with B-cell Chronic Lymphocytic Leukemia CLL, run by French Innovative Leukemia Organisation at 2 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
B-cell Chronic Lymphocytic Leukemia CLL
What is being tested?
Rituximab, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
2 sitesFrance
Study dates
May 2011to Mar 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Guillaume CARTRON

    Montpellier, Regional University Hospital, 34295

  • Stephane LEPRETRE

    Rouen, CLCC Henri Becquerel, 76038

Other trials in France

About this study

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

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

Read the 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.

Keywords
B CLL, Fist line treatment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called R

    • 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

  • RituximabDrug

    Also called R

    • 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

  • CyclophosphamideDrug

    Also called C

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

  • FludarabineDrug

    Also called F

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

Study groups in NCT01370772
Study groupRoleWhat they receive
Standard R-FC armActive comparatorStandard 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
Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine
DenseR-FC armExperimentalDenseR-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
Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 9 months

Secondary outcomes (9)

  1. To determine and compare the progression free survival PFS

    Measured: 3 years

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

    Treatment evaluation

    Measured: 9 months

  3. To evaluate FcyRs polymorphisms influence on clinical response

    R Dense arm treatment evaluation

    Measured: 9 months

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

    Measured: 12 months

  5. To evaluate the safety profile of higher doses of rituximab

    5 months treatment and 36 months follow up

    Measured: 41

  6. To determine the event-free survival EFS

    Measured: 3 years

  7. To determine and compare the disease-free survival DFS

    Measured: 3 years

  8. To determine the overall survival OS

    Measured: 3 years

  9. To determine the time to next treatment TTNT

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionSep 2014
  4. Study completionMar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01370772
Sponsor's protocol ID
CLL 2010 FMP
Status last verified
Mar 2016
First submitted
23 May 2011
Last updated
16 Mar 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 36325355

  • 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.

    PubMed 28126961

  • 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.

    PubMed 27783363

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab, Cyclophosphamide and Fludarabine in people with B-cell Chronic Lymphocytic Leukemia CLL, run by French Innovative Leukemia Organisation at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease (time frame: 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01370772, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2016.

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