Clinical trial NCT00281892: Fludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia
Official title: Darbepoetin Alfa in Patients With Chronic Lymphocytic Leukemia and Comorbidity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Anemia
Keywords: anemia
refractory 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
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2006-01-25
Enrollment: 97
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Event-free survival
timeFrame: up to 24 months after the last dose of study medication
Secondary outcomes:
measure: Response Rate
timeFrame: 2 months after the end of the last cycle
measure: toxicity
timeFrame: 28 days after the end of the last cycle
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
city: Bad Soden
country: Germany
facility: Onkologische Schwerpunktpraxis und Tagesklinik Dres
city: Berlin
country: Germany
facility: Internistische Gemeinschaftspraxis - Berlin
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Dusseldorf
country: Germany
facility: Internistische Praxis - Dusseldorf
city: Emden
country: Germany
facility: Hans - Susemihl - Krankenhaus
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Gerlingen
country: Germany
facility: Internistische Praxis - Gerlingen
city: Germering
country: Germany
facility: Internistische Praxisgemeinschaft
city: Göttingen
country: Germany
facility: Universitaetsklinikum Göttingen
city: Halle
country: Germany
facility: Internistische Gemeinschaftspraxis - Halle
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Kempten
country: Germany
facility: Klinikum Kempten Oberallgaeu
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Landshut
country: Germany
facility: Internistische Praxis - Landshut
city: Lebach
country: Germany
facility: Caritas - Krakenhaus Lebach
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Magdeburg
country: Germany
facility: Staedtisches Klinikum Magdeburg
city: Monchengladbach
country: Germany
facility: Hospital Maria-Hilf II
city: Munchen
country: Germany
facility: Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Munich
country: Germany
facility: I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Haematologische Schwerpunktpraxis
city: Mutlangen
country: Germany
facility: Klinikum Schwaebisch Gmuend Stauferklinik
city: München
country: Germany
facility: Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier
city: Neunkirchen
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Schmidt
city: Norderstedt
country: Germany
facility: Praxis fuer Haematologie und Interne Onkologie
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Pforzheim
country: Germany
city: Regensburg
country: Germany
facility: Scherpunktpraxis fur Hematologie und Onkologie
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brueder Regensburg
city: Saarbruecken
country: Germany
facility: Schwerpunktpraxis fuer Haematologie und Onkologie
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Vechta
country: Germany
facility: St. Marienhospital - Vechta
city: Weiden
country: Germany
facility: Haematologische Praxis
city: Wuppertal
country: Germany
facility: Helios Kliniken Wuppertal University Hospital
city: Wurzburg
country: Germany
facility: Hamatologisch - Onkologische Praxis Wurzburg
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Michael Hallek, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.