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

Anemia Clinical Trial

Official title:

Darbepoetin Alfa in Patients With Chronic Lymphocytic Leukemia and Comorbidity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00281892
• Other study ID #: CLL9
• Secondary ID: GCLLSG-CLL9EU-20
• Status: Completed
• Phase: Phase 3
• Start date: September 2004
• Est. completion date: October 2010

Study information

• Verified date: May 2018
• Source: German CLL Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: October 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• 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

Drug:
• 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.

Locations

Country	Name	City	State
Germany	Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg	Augsburg
Germany	Onkologische Schwerpunktpraxis und Tagesklinik Dres	Bad Soden
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Internistische Gemeinschaftspraxis - Berlin	Berlin
Germany	Augusta-Kranken-Anstalt gGmbH	Bochum
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Internistische Praxis - Dusseldorf	Dusseldorf
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	Monchengladbach
Germany	Hamatologie/Onkologie Praxisgemeinschaft - Muenchen	Munchen
Germany	Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier	München
Germany	Haematologische Schwerpunktpraxis	Munich
Germany	I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen	Munich
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Munich Oncologic Practice at Elisenhof	Munich
Germany	Klinikum Schwaebisch Gmuend Stauferklinik	Mutlangen
Germany	Onkologische Schwerpunktpraxis Dr. Schmidt	Neunkirchen
Germany	Praxis fuer Haematologie und Interne Onkologie	Norderstedt
Germany	Internistische Gemeinschaftspraxis - Oldenburg	Oldenburg
Germany	Krankenhaus Barmherzige Brueder Regensburg	Regensburg
Germany	Scherpunktpraxis fur Hematologie und Onkologie	Regensburg
Germany	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbruecken
Germany	St. Marien - Krankenhaus Siegen GMBH	Siegen
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
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	Wurzburg

Sponsors (1)

Lead Sponsor	Collaborator
German CLL Study Group

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Goede V, Bahlo J, Chataline V, Eichhorst B, Dürig 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 L — View Citation

Goede V, Busch R, Bahlo J, Chataline V, Kremers S, Müller 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 com — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	defined as the time from initial randomization/stratification to the time-point of progressive disease, new therapy, or death)	up to 24 months after the last dose of study medication
Secondary	Response Rate	Restaging after the end of treatment included evaluation of the peripheral blood and physical examination; use of imaging techniques (ultrasound and conventional radiography or computertomography) and evaluation of the bone marrow were mandatory to assign a complete remission	2 months after the end of the last cycle
Secondary	toxicity	adverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0).	28 days after the end of the last cycle

External Links

•   Click here for more information about this study: CLL9 (German CLL Study Group)