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

NCT00769522 | Completed Phase 3 DMC

• 3 other identifiers: CLL10CDR00006161692007-007587-21
• Study Type: interventional
• Target: 564
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Lymphocytic Leukemia

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate after 24 months

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

  2008-2015

Secondary Outcomes (9)

• Minimal residual disease, complete response rates, and partial response rates

  2008-2015

• Duration of remission

  2008-2015

• Event-free survival

  2008-2015

• Overall survival

  2008-2015

• Overall response rate

  2008-2015

Study Arms (2)

FCR

EXPERIMENTAL

Biological: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

BR

EXPERIMENTAL

Biological: Rituximab; Drug: Bendamustine

Interventions

Rituximab BIOLOGICAL

cycle 1: 375 mg/m² i.v., day 0, q28d cycle 2-6: 500 mg/m² i.v., day 1, q28d

Also known as: Mabthera, Rituxan

BR; FCR

Bendamustine DRUG

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

Also known as: Levact, Ribomustin, Treanda

BR

Cyclophosphamide DRUG

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

Also known as: Endoxan

FCR

Fludarabine DRUG

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

Also known as: Fludura

FCR

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• German CLL Study Group: lead
• Roche Pharma AG: collaborator
• Mundipharma Pte Ltd.: collaborator

Study Sites (1)

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, D-50924, Germany

Location

Related Publications (6)

• 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.

  PMID: 31280963 BACKGROUND

• 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.

  PMID: 29255066 BACKGROUND

• 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.

  PMID: 39050548 BACKGROUND

• 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.

  PMID: 27216274 BACKGROUND

• 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.

  PMID: 27573660 BACKGROUND

• 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.

  PMID: 28745332 BACKGROUND

Related Links

• Click here for more information about this study: CLL10 (German CLL Study Group)

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab; Bendamustine Hydrochloride; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Officials

• Barbara Eichhorst, MD

  Medizinische Universitaetsklinik I at the University of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: October 2, 2008
• Primary Completion: July 1, 2011
• Study Completion: January 1, 2018
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)