Fludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT00281892

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2010-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Darbepoetin alfa may cause the body to make more red blood cells. It is not yet known whether fludarabine is more effective with or without darbepoetin alfa in treating chronic lymphocytic leukemia.

PURPOSE: This phase III trial is studying fludarabine to see how well it works when given together with or without darbepoetin alfa in treating older patients with chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

• Compare the efficacy of fludarabine with or without darbepoetin alfa in geriatric patients with chronic lymphocytic leukemia and relevant comorbidities.
• Determine the effect of these regimens in reducing anemia, lowering the requirements of transfusion, and reducing the duration and frequency of hospitalization in these patients.
• Determine the quality of life of patients treated with these regimens.
• Determine event-free, progression-free, and overall survival of patients treated with these regimens.
• Evaluate the medical-economical aspects of these regimens in these patients

OUTLINE: This is a multicenter study. Patients are stratified according to hemoglobin value (< 12 g/dL [stratum 1] vs > 12 g/dL [stratum 2]). Patients are assigned to 1 of 2 treatment strata.

• Stratum 1: Patients receive fludarabine IV on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses. Patients also receive darbepoetin alfa subcutaneously once weekly for up to 6 weeks.
• Stratum 2: Patients receive fludarabine as in stratum 1. Quality of life is evaluated periodically.

PROJECTED ACCRUAL: A total of 348 patients will be accrued for this study.

Conditions

Chronic Lymphocytic Leukemia; Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine plus Darbopoetin

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles and 500 mcg of darbepoetin alfa subcutaneously every 3 weeks

Group Type: EXPERIMENTAL

Fludarabine plus Darbopoetin

Intervention Type: BIOLOGICAL

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles and 500 mcg of darbepoetin alfa subcutaneously every 3 weeks

fludarabine mono

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles with no additional growth factor support.

Group 2 - Patients with an initial Hb-value more than 12 g/dl start to receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles . Patients of group 2 will be eventually randomized at later timepoints, if the Hb-value drops below 12 g/dl. Randomized patients will receive either 500 mcg darbepoetin alfa subcutaneously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.

Group Type: ACTIVE_COMPARATOR

Fludarabine mono

Intervention Type: DRUG

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles with no additional growth factor support.

Group 2 - Patients with an initial Hb-value more than 12 g/dl start to receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles . Patients of group 2 will be eventually randomized at later timepoints, if the Hb-value drops below 12 g/dl. Randomized patients will receive either 500 mcg darbepoetin alfa subcutaneously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.

Interventions

Fludarabine plus Darbopoetin

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles and 500 mcg of darbepoetin alfa subcutaneously every 3 weeks

Intervention Type: BIOLOGICAL

Fludarabine mono

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles with no additional growth factor support.

Group 2 - Patients with an initial Hb-value more than 12 g/dl start to receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles . Patients of group 2 will be eventually randomized at later timepoints, if the Hb-value drops below 12 g/dl. Randomized patients will receive either 500 mcg darbepoetin alfa subcutaneously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:

• Previously untreated disease
• Progressive or relapsed CLL after treatment with nonpurine analog-containing regimens as chlorambucil or bendamustine hydrochloride
• Meets 1 of the following staging criteria:

• Binet stage A disease with B symptoms requiring treatment
• Binet stage B disease requiring treatment, meeting ≥ 1 of the following criteria:

• Rapid disease progression
• Enlarged lymph nodes and organs
• Severe B symptoms
• Binet stage C disease
• Must have comorbidities (i.e., CIRS score > 6)
• Must have restricted kidney function (i.e., creatinine clearance < 70mL/min)
• No transformation to aggressive non-Hodgkin's lymphoma (Richter's syndrome)

PATIENT CHARACTERISTICS:

• Life expectancy > 6 months
• Creatinine clearance > 30 mL/min
• No active second malignancy
• No active bacterial, viral, or fungal infection
• No conditions that would preclude substitution of iron
• No severe myocardial, coronary, or respiratory insufficiency
• No severe liver insufficiency
• No known hypersensitivity to darbepoetin alfa
• No cerebral dysfunction that would preclude participation in the required study procedures

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent participation in another clinical trial

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hallek, MD

Role: STUDY_CHAIR

Medizinische Universitaetsklinik I at the University of Cologne

Locations

Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg

Augsburg, , Germany

Onkologische Schwerpunktpraxis und Tagesklinik Dres

Bad Soden, , Germany

Internistische Gemeinschaftspraxis - Berlin

Berlin, , Germany

Charite - Campus Charite Mitte

Berlin, , Germany

Augusta-Kranken-Anstalt gGmbH

Bochum, , Germany

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Internistische Praxis - Dusseldorf

Düsseldorf, , Germany

Hans - Susemihl - Krankenhaus

Emden, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), , Germany

Internistische Praxis - Gerlingen

Gerlingen, , Germany

Internistische Praxisgemeinschaft

Germering, , Germany

Universitaetsklinikum Göttingen

Göttingen, , Germany

Internistische Gemeinschaftspraxis - Halle

Halle, , Germany

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

Klinikum Kempten Oberallgaeu

Kempten, , Germany

Internistische Onkologische Praxis - Kronach

Kronach, , Germany

Internistische Praxis - Landshut

Landshut, , Germany

Caritas - Krakenhaus Lebach

Lebach, , Germany

Onkologische Schwerpunktpraxis - Leer

Leer, , Germany

Staedtisches Klinikum Magdeburg

Magdeburg, , Germany

Hospital Maria-Hilf II

Mönchengladbach, , Germany

Munich Oncologic Practice at Elisenhof

Munich, , Germany

I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen

Munich, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Haematologische Schwerpunktpraxis

Munich, , Germany

Klinikum Schwaebisch Gmuend Stauferklinik

Mutlangen, , Germany

Hamatologie/Onkologie Praxisgemeinschaft - Muenchen

München, , Germany

Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier

München, , Germany

Onkologische Schwerpunktpraxis Dr. Schmidt

Neunkirchen, , Germany

Praxis fuer Haematologie und Interne Onkologie

Norderstedt, , Germany

Internistische Gemeinschaftspraxis - Oldenburg

Oldenburg, , Germany

Pforzheim, , Germany

Scherpunktpraxis fur Hematologie und Onkologie

Regensburg, , Germany

Krankenhaus Barmherzige Brueder Regensburg

Regensburg, , Germany

Schwerpunktpraxis fuer Haematologie und Onkologie

Saarbrücken, , Germany

St. Marien - Krankenhaus Siegen GMBH

Siegen, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, , Germany

St. Marienhospital - Vechta

Vechta, , Germany

Haematologische Praxis

Weiden, , Germany

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Hamatologisch - Onkologische Praxis Wurzburg

Würzburg, , Germany

Countries

Germany

References

Goede V, Busch R, Bahlo J, Chataline V, Kremers S, Muller L, Reschke D, Schlag R, Schmidt B, Vehling-Kaiser U, Wedding U, Stilgenbauer S, Hallek M. Low-dose fludarabine with or without darbepoetin alfa in patients with chronic lymphocytic leukemia and comorbidity: primary results of the CLL9 trial of the German CLL Study Group. Leuk Lymphoma. 2016;57(3):596-603. doi: 10.3109/10428194.2015.1079314. Epub 2015 Oct 12.

Reference Type: RESULT

PMID: 26293380 (View on PubMed)

Goede V, Bahlo J, Chataline V, Eichhorst B, Durig J, Stilgenbauer S, Kolb G, Honecker F, Wedding U, Hallek M. Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group. Leuk Lymphoma. 2016;57(4):789-96. doi: 10.3109/10428194.2015.1091933. Epub 2015 Oct 13.

Reference Type: RESULT

PMID: 26377031 (View on PubMed)

Other Identifiers

GCLLSG-CLL9

Identifier Type: -

Identifier Source: secondary_id

EU-20561

Identifier Type: -

Identifier Source: secondary_id

AMGEN-GCLLSG-CLL9

Identifier Type: -

Identifier Source: secondary_id

2005-003014-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLL9

Identifier Type: -

Identifier Source: org_study_id