Back to resultsFludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia
Primary Purpose
Chronic Lymphocytic Leukemia, Anemia
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Fludarabine plus Darbopoetin
Fludarabine mono
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring 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
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
Sites / Locations
- Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
- Onkologische Schwerpunktpraxis und Tagesklinik Dres
- Internistische Gemeinschaftspraxis - Berlin
- Charite - Campus Charite Mitte
- Augusta-Kranken-Anstalt gGmbH
- Medizinische Universitaetsklinik I at the University of Cologne
- Internistische Praxis - Dusseldorf
- Hans - Susemihl - Krankenhaus
- Universitaetsklinikum Essen
- Klinikum Frankfurt (Oder) GmbH
- Internistische Praxis - Gerlingen
- Internistische Praxisgemeinschaft
- Universitaetsklinikum Göttingen
- Internistische Gemeinschaftspraxis - Halle
- University Medical Center Hamburg - Eppendorf
- Clinic for Bone Marrow Transplantation and Hematology and Oncology
- Westpfalz-Klinikum GmbH
- Staedtisches Klinikum Karlsruhe gGmbH
- Klinikum Kempten Oberallgaeu
- Internistische Onkologische Praxis - Kronach
- Internistische Praxis - Landshut
- Caritas - Krakenhaus Lebach
- Onkologische Schwerpunktpraxis - Leer
- Staedtisches Klinikum Magdeburg
- Hospital Maria-Hilf II
- Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
- Munich Oncologic Practice at Elisenhof
- I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
- Klinikum der Universitaet Muenchen - Grosshadern Campus
- Haematologische Schwerpunktpraxis
- Klinikum Schwaebisch Gmuend Stauferklinik
- Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier
- Onkologische Schwerpunktpraxis Dr. Schmidt
- Praxis fuer Haematologie und Interne Onkologie
- Internistische Gemeinschaftspraxis - Oldenburg
- Scherpunktpraxis fur Hematologie und Onkologie
- Krankenhaus Barmherzige Brueder Regensburg
- Schwerpunktpraxis fuer Haematologie und Onkologie
- St. Marien - Krankenhaus Siegen GMBH
- Southwest German Cancer Center at Eberhard-Karls-University
- Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
- St. Marienhospital - Vechta
- Haematologische Praxis
- Helios Kliniken Wuppertal University Hospital
- Hamatologisch - Onkologische Praxis Wurzburg
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fludarabine plus Darbopoetin
fludarabine mono
Arm Description
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 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.
Outcomes
Primary Outcome Measures
Event-free survival
defined as the time from initial randomization/stratification to the time-point of progressive disease, new therapy, or death)
Secondary Outcome Measures
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
toxicity
adverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00281892
Brief Title
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
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
September 2004 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
German CLL Study Group
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fludarabine plus Darbopoetin
Arm Type
Experimental
Arm Description
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
Arm Title
fludarabine mono
Arm Type
Active Comparator
Arm Description
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
Biological
Intervention Name(s)
Fludarabine plus Darbopoetin
Intervention Description
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
Drug
Intervention Name(s)
Fludarabine mono
Intervention Description
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.
Primary Outcome Measure Information:
Title
Event-free survival
Description
defined as the time from initial randomization/stratification to the time-point of progressive disease, new therapy, or death)
Time Frame
up to 24 months after the last dose of study medication
Secondary Outcome Measure Information:
Title
Response Rate
Description
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
Time Frame
2 months after the end of the last cycle
Title
toxicity
Description
adverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0).
Time Frame
28 days after the end of the last cycle
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Hallek, MD
Organizational Affiliation
Medizinische Universitaetsklinik I at the University of Cologne
Official's Role
Study Chair
Facility Information:
Facility Name
Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
City
Augsburg
ZIP/Postal Code
86150
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis und Tagesklinik Dres
City
Bad Soden
ZIP/Postal Code
65812
Country
Germany
Facility Name
Internistische Gemeinschaftspraxis - Berlin
City
Berlin
ZIP/Postal Code
13347
Country
Germany
Facility Name
Charite - Campus Charite Mitte
City
Berlin
ZIP/Postal Code
D-10117
Country
Germany
Facility Name
Augusta-Kranken-Anstalt gGmbH
City
Bochum
ZIP/Postal Code
D-44791
Country
Germany
Facility Name
Medizinische Universitaetsklinik I at the University of Cologne
City
Cologne
ZIP/Postal Code
D-50924
Country
Germany
Facility Name
Internistische Praxis - Dusseldorf
City
Dusseldorf
ZIP/Postal Code
40211
Country
Germany
Facility Name
Hans - Susemihl - Krankenhaus
City
Emden
ZIP/Postal Code
D-26721
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
D-45122
Country
Germany
Facility Name
Klinikum Frankfurt (Oder) GmbH
City
Frankfurt (Oder)
ZIP/Postal Code
D-15236
Country
Germany
Facility Name
Internistische Praxis - Gerlingen
City
Gerlingen
ZIP/Postal Code
70839
Country
Germany
Facility Name
Internistische Praxisgemeinschaft
City
Germering
ZIP/Postal Code
82110
Country
Germany
Facility Name
Universitaetsklinikum Göttingen
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Internistische Gemeinschaftspraxis - Halle
City
Halle
ZIP/Postal Code
06110
Country
Germany
Facility Name
University Medical Center Hamburg - Eppendorf
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
Clinic for Bone Marrow Transplantation and Hematology and Oncology
City
Idar-Oberstein
ZIP/Postal Code
D-55743
Country
Germany
Facility Name
Westpfalz-Klinikum GmbH
City
Kaiserslautern
ZIP/Postal Code
D-67653
Country
Germany
Facility Name
Staedtisches Klinikum Karlsruhe gGmbH
City
Karlsruhe
ZIP/Postal Code
76133
Country
Germany
Facility Name
Klinikum Kempten Oberallgaeu
City
Kempten
ZIP/Postal Code
D-87439
Country
Germany
Facility Name
Internistische Onkologische Praxis - Kronach
City
Kronach
ZIP/Postal Code
96317
Country
Germany
Facility Name
Internistische Praxis - Landshut
City
Landshut
ZIP/Postal Code
84028
Country
Germany
Facility Name
Caritas - Krakenhaus Lebach
City
Lebach
ZIP/Postal Code
66822
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis - Leer
City
Leer
ZIP/Postal Code
D-26789
Country
Germany
Facility Name
Staedtisches Klinikum Magdeburg
City
Magdeburg
ZIP/Postal Code
D-39130
Country
Germany
Facility Name
Hospital Maria-Hilf II
City
Monchengladbach
ZIP/Postal Code
D-41063
Country
Germany
Facility Name
Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
City
Munchen
ZIP/Postal Code
81245
Country
Germany
Facility Name
Munich Oncologic Practice at Elisenhof
City
Munich
ZIP/Postal Code
D-80335
Country
Germany
Facility Name
I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen - Grosshadern Campus
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Haematologische Schwerpunktpraxis
City
Munich
ZIP/Postal Code
D-81679
Country
Germany
Facility Name
Klinikum Schwaebisch Gmuend Stauferklinik
City
Mutlangen
ZIP/Postal Code
D-73557
Country
Germany
Facility Name
Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier
City
München
ZIP/Postal Code
D-81241
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis Dr. Schmidt
City
Neunkirchen
ZIP/Postal Code
D-66538
Country
Germany
Facility Name
Praxis fuer Haematologie und Interne Onkologie
City
Norderstedt
ZIP/Postal Code
22844
Country
Germany
Facility Name
Internistische Gemeinschaftspraxis - Oldenburg
City
Oldenburg
ZIP/Postal Code
D-26121
Country
Germany
City
Pforzheim
ZIP/Postal Code
75179
Country
Germany
Facility Name
Scherpunktpraxis fur Hematologie und Onkologie
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Krankenhaus Barmherzige Brueder Regensburg
City
Regensburg
ZIP/Postal Code
D-93049
Country
Germany
Facility Name
Schwerpunktpraxis fuer Haematologie und Onkologie
City
Saarbruecken
ZIP/Postal Code
66113
Country
Germany
Facility Name
St. Marien - Krankenhaus Siegen GMBH
City
Siegen
ZIP/Postal Code
D-57072
Country
Germany
Facility Name
Southwest German Cancer Center at Eberhard-Karls-University
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
D-89081
Country
Germany
Facility Name
St. Marienhospital - Vechta
City
Vechta
ZIP/Postal Code
D-49377
Country
Germany
Facility Name
Haematologische Praxis
City
Weiden
ZIP/Postal Code
D-92637
Country
Germany
Facility Name
Helios Kliniken Wuppertal University Hospital
City
Wuppertal
ZIP/Postal Code
D-42283
Country
Germany
Facility Name
Hamatologisch - Onkologische Praxis Wurzburg
City
Wurzburg
ZIP/Postal Code
97070
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26293380
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.
Results Reference
result
PubMed Identifier
26377031
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.
Results Reference
result
Links:
URL
http://www.dcllsg.de/en/trial/cll9/
Description
Click here for more information about this study: CLL9 (German CLL Study Group)
Learn more about this trial
Fludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia
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