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Chronic Lymphocytic LeukemiaPhase 3NCT00769522

FCR or BR in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia

A Phase 3 study testing Rituximab, Bendamustine and Cyclophosphamide in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.

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

RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Rituximab, Bendamustine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
564 participants
Where
1 siteGermany
Study dates
2 Oct 2008to Jan 2018
Phase
Phase 3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:
  • Binet stage C disease or stage B or A disease requiring treatment
  • Binet stage B or A disease meeting ≥ 1 of the following:
  • B-symptoms (e.g., night sweats, weight loss ≥ 10% within the past 6 months, fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection) or constitutional symptoms (e.g., fatigue)
  • Progressive lymphocytosis, defined as peripheral lymphocyte count > 5 x 10^9/L (i.e., > 50% increase over a 2-month period or doubling of peripheral blood lymphocyte count < 6 months)
  • Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia
  • Massive, progressive, or painful splenomegaly or hypersplenism
  • Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
  • No 17p deletion by FISH
  • No aggressive B-cell cancer, such as Richter syndrome

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy ≥ 6 months
  • Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless directly attributable to CLL)
  • AST and ALT ≤ 2 times ULN (unless directly attributable to CLL)
  • Creatinine clearance ≥ 70 mL/min (creatinine clearance is to be calculated only in patients with serum creatinine ≥ 1.1 mg/dL)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
  • Hepatitis B and C negative
  • HIV negative
  • CIRS score > 6 or a single score of 4 for one organ category
  • No active secondary malignancy requiring treatment, except basal cell carcinoma or malignant tumor curatively treated by surgery, or successfully treated secondary malignancies in complete remission > 5 years prior to enrollment
  • No history of anaphylaxis following exposure to monoclonal antibodies
  • No active bacterial, viral, or fungal infection
  • No medical condition requiring prolonged use of oral corticosteroids (i.e., > 1 month)
  • No cerebral dysfunction or legal incapacity
  • No circumstance that would preclude completion of the study or the required follow-up

PRIOR CONCURRENT THERAPY:

  • No prior CLL specific-chemotherapy, radiotherapy, and/or immunotherapy
  • Prednisolone administered immediately prior to initiation of study therapy allowed for very high lymphocyte counts
  • No concurrent participation in another clinical trial

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Medizinische Universitaetsklinik I at the University of Cologne

    Cologne, D-50924

Other trials in Germany

About this study

Official title: Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Bendamustine and Rituximab (BR) in Patients With Previously Untreated Chronic Lymphocytic Leukaemia

RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving bendamustine together with rituximab in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia.

Read the detailed description

OBJECTIVES:

  • To compare the therapeutic efficacy of fludarabine phosphate, cyclophosphamide, and rituximab vs bendamustine hydrochloride and rituximab in patients with previously untreated B-cell chronic lymphocytic leukemia.
  • To compare the incidence of major side effects (e.g., myelosuppression) associated with these regimens in these patients.
  • To compare the rate of infections and secondary neoplasias in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to country and disease stage. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive fludarabine phosphate IV and cyclophosphamide IV on days 1-3. Patients also receive rituximab IV on day 0 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive bendamustine hydrochloride IV on days 1 and 2. Patients also receive rituximab as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires (EORTC-C30 and EURO-QOL) at baseline and then at 12, 24, 36, 48, and 60 months.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter.

Keywords
B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • RituximabBiological

    Also called Mabthera, Rituxan

    cycle 1: 375 mg/m² i.v., day 0, q28d

    cycle 2-6: 500 mg/m² i.v., day 1, q28d

  • BendamustineDrug

    Also called Levact, Ribomustin, Treanda

    cycle 1-6: 90mg/m² i.v., day 1-2, q28d

  • CyclophosphamideDrug

    Also called Endoxan

    cycle 1-6: 250 mg/m² i.v., days 1-3, q28d

  • FludarabineDrug

    Also called Fludura

    cycle 1-6: 25 mg/m² i.v., days 1-3, q28d

Study groups in NCT00769522
Study groupRoleWhat they receive
FCRExperimentalNot described
Receives: Biological: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine
BRExperimentalNot described
Receives: Biological: Rituximab; Drug: Bendamustine

What is being measured

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

  1. Progression-free survival rate after 24 months

    estimated time point when 198 needed events for the final analysis(PD or deaths) have occured.

    Measured: 2008-2015

Secondary outcomes (9)

  1. Minimal residual disease, complete response rates, and partial response rates

    done within the final analysis

    Measured: 2008-2015

  2. Duration of remission

    done within the final analysis

    Measured: 2008-2015

  3. Event-free survival

    done within the final analysis

    Measured: 2008-2015

  4. Overall survival

    done within the final analysis

    Measured: 2008-2015

  5. Overall response rate

    done within the final analysis

    Measured: 2008-2015

  6. Response rates in and survival times in biological subgroups

    done within the final analysis

    Measured: 2008-2015

  7. Toxicity rates

    done within the final analysis

    Measured: 2008-2015

  8. Quality of life

    done within the final analysis

    Measured: 2008-2015

  9. Standard safety analysis

    done within the final analysis

    Measured: 2008-2015

Timeline

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

  1. First posted9 Oct 2008 (estimated)
  2. Study start2 Oct 2008
  3. Primary completionJul 2011
  4. Study completionJan 2018

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
564 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00769522
Sponsor's protocol ID
CLL10
Other IDs
CDR0000616169, 2007-007587-21
Status last verified
Dec 2024
First submitted
8 Oct 2008
Last updated
31 Dec 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Kurtz DM, Esfahani MS, Scherer F, Soo J, Jin MC, Liu CL, Newman AM, Duhrsen U, Huttmann A, Casasnovas O, Westin JR, Ritgen M, Bottcher S, Langerak AW, Roschewski M, Wilson WH, Gaidano G, Rossi D, Bahlo J, Hallek M, Tibshirani R, Diehn M, Alizadeh AA. Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction. Cell. 2019 Jul 25;178(3):699-713.e19. doi: 10.1016/j.cell.2019.06.011. Epub 2019 Jul 4.

    PubMed 31280963

  • Dimier N, Delmar P, Ward C, Morariu-Zamfir R, Fingerle-Rowson G, Bahlo J, Fischer K, Eichhorst B, Goede V, van Dongen JJM, Ritgen M, Bottcher S, Langerak AW, Kneba M, Hallek M. A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL. Blood. 2018 Mar 1;131(9):955-962. doi: 10.1182/blood-2017-06-792333. Epub 2017 Dec 18.

    PubMed 29255066

  • Kutsch N, Robrecht S, Fink A, Lange E, Weide R, Kiehl MG, Sokler M, Schlag R, Vehling-Kaiser U, Kochling G, Ploger C, Gregor M, Plesner T, Clausen MR, Oschlies I, Ritgen M, Herling M, Fischer K, Dohner H, Wendtner CM, Kreuzer KA, Stilgenbauer S, Hallek M, Bottcher S, Klapper W, Eichhorst B. The role of trephine bone marrow biopsies in the era of measurable residual disease-Results from the CLL10 trial of the German CLL Study Group (GCLLSG). Hemasphere. 2024 Jul 24;8(7):e126. doi: 10.1002/hem3.126. eCollection 2024 Jul. No abstract available.

    PubMed 39050548

  • Eichhorst B, Fink AM, Bahlo J, Busch R, Kovacs G, Maurer C, Lange E, Koppler H, Kiehl M, Sokler M, Schlag R, Vehling-Kaiser U, Kochling G, Ploger C, Gregor M, Plesner T, Trneny M, Fischer K, Dohner H, Kneba M, Wendtner CM, Klapper W, Kreuzer KA, Stilgenbauer S, Bottcher S, Hallek M; international group of investigators; German CLL Study Group (GCLLSG). First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016 Jul;17(7):928-942. doi: 10.1016/S1470-2045(16)30051-1. Epub 2016 May 20.

    PubMed 27216274

  • Kovacs G, Robrecht S, Fink AM, Bahlo J, Cramer P, von Tresckow J, Maurer C, Langerbeins P, Fingerle-Rowson G, Ritgen M, Kneba M, Dohner H, Stilgenbauer S, Klapper W, Wendtner CM, Fischer K, Hallek M, Eichhorst B, Bottcher S. Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. J Clin Oncol. 2016 Nov 1;34(31):3758-3765. doi: 10.1200/JCO.2016.67.1305.

    PubMed 27573660

  • Al-Sawaf O, Robrecht S, Bahlo J, Fink AM, Cramer P, von Tresckow J, Maurer C, Bergmann M, Seiler T, Lange E, Kneba M, Stilgenbauer S, Dohner H, Kiehl MG, Jager U, Wendtner CM, Fischer K, Goede V, Hallek M, Eichhorst B, Hopfinger G. Impact of gender on outcome after chemoimmunotherapy in patients with chronic lymphocytic leukemia: a meta-analysis by the German CLL study group. Leukemia. 2017 Oct;31(10):2251-2253. doi: 10.1038/leu.2017.221. Epub 2017 Jul 12. No abstract available.

    PubMed 28745332

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab, Bendamustine and Cyclophosphamide in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.

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

Who may be eligible to take part?

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 31 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Progression-free survival rate after 24 months (time frame: 2008-2015). 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 NCT00769522, which also lists 6 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 31 Dec 2024.

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