Fludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia (CDR0000454570)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
German CLL Study Group
ClinicalTrials.gov Identifier:
NCT00281892
First received: January 24, 2006
Last updated: August 10, 2016
Last verified: August 2016
  Purpose

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.


Condition Intervention Phase
Anemia
Leukemia
Biological: Fludarabine plus Darbopoetin
Drug: Fludarabine mono
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Darbepoetin Alfa in Patients With Chronic Lymphocytic Leukemia and Comorbidity

Resource links provided by NLM:


Further study details as provided by German CLL Study Group:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: up to 24 months after the last dose of study medication ] [ Designated as safety issue: No ]
    defined as the time from initial randomization/stratification to the time-point of progressive disease, new therapy, or death)


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 2 months after the end of the last cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 days after the end of the last cycle ] [ Designated as safety issue: Yes ]
    dverse events were reported according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC version 2.0).


Enrollment: 97
Study Start Date: September 2004
Study Completion Date: October 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 subcutanously every 3 weeks
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 subcutanously every 3 weeks
Active Comparator: 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 inital 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 subcutanously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.

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 inital 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 subcutanously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.


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

Ages Eligible for Study:   up to 120 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281892

Locations
Germany
Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg
Augsburg, Germany, 86150
Onkologische Schwerpunktpraxis und Tagesklinik Dres
Bad Soden, Germany, 65812
Internistische Gemeinschaftspraxis - Berlin
Berlin, Germany, 13347
Charite - Campus Charite Mitte
Berlin, Germany, D-10117
Augusta-Kranken-Anstalt gGmbH
Bochum, Germany, D-44791
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany, D-50924
Internistische Praxis - Dusseldorf
Dusseldorf, Germany, 40211
Hans - Susemihl - Krankenhaus
Emden, Germany, D-26721
Universitaetsklinikum Essen
Essen, Germany, D-45122
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), Germany, D-15236
Internistische Praxis - Gerlingen
Gerlingen, Germany, 70839
Internistische Praxisgemeinschaft
Germering, Germany, 82110
Universitaetsklinikum Goettingen
Goettingen, Germany, D-37075
Internistische Gemeinschaftspraxis - Halle
Halle, Germany, 06110
University Medical Center Hamburg - Eppendorf
Hamburg, Germany, D-20246
Clinic for Bone Marrow Transplantation and Hematology and Oncology
Idar-Oberstein, Germany, D-55743
Westpfalz-Klinikum GmbH
Kaiserslautern, Germany, D-67653
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany, 76133
Klinikum Kempten Oberallgaeu
Kempten, Germany, D-87439
Internistische Onkologische Praxis - Kronach
Kronach, Germany, 96317
Internistische Praxis - Landshut
Landshut, Germany, 84028
Caritas - Krakenhaus Lebach
Lebach, Germany, 66822
Onkologische Schwerpunktpraxis - Leer
Leer, Germany, D-26789
Staedtisches Klinikum Magdeburg
Magdeburg, Germany, D-39130
Hospital Maria-Hilf II
Monchengladbach, Germany, D-41063
Hamatologie/Onkologie Praxisgemeinschaft - Muenchen
Munchen, Germany, 81245
Munich Oncologic Practice at Elisenhof
Munich, Germany, D-80335
I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
Munich, Germany, D-81377
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, Germany, D-81377
Haematologische Schwerpunktpraxis
Munich, Germany, D-81679
Klinikum Schwaebisch Gmuend Stauferklinik
Mutlangen, Germany, D-73557
Haematologische-onkologische GemeinschaftspraxisSchick - Schick - Schmidt - Wiesmeier
München, Germany, D-81241
Onkologische Schwerpunktpraxis Dr. Schmidt
Neunkirchen, Germany, D-66538
Praxis fuer Haematologie und Interne Onkologie
Norderstedt, Germany, 22844
Internistische Gemeinschaftspraxis - Oldenburg
Oldenburg, Germany, D-26121
Pforzheim, Germany, 75179
Scherpunktpraxis fur Hematologie und Onkologie
Regensburg, Germany, 93053
Krankenhaus Barmherzige Brueder Regensburg
Regensburg, Germany, D-93049
Schwerpunktpraxis fuer Haematologie und Onkologie
Saarbruecken, Germany, 66113
St. Marien - Krankenhaus Siegen GMBH
Siegen, Germany, D-57072
Southwest German Cancer Center at Eberhard-Karls-University
Tuebingen, Germany, D-72076
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, Germany, D-89081
St. Marienhospital - Vechta
Vechta, Germany, D-49377
Haematologische Praxis
Weiden, Germany, D-92637
Helios Kliniken Wuppertal University Hospital
Wuppertal, Germany, D-42283
Hamatologisch - Onkologische Praxis Wurzburg
Wurzburg, Germany, 97070
Sponsors and Collaborators
German CLL Study Group
Investigators
Study Chair: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne
  More Information

Responsible Party: German CLL Study Group
ClinicalTrials.gov Identifier: NCT00281892     History of Changes
Other Study ID Numbers: CLL9  GCLLSG-CLL9  EU-20561  AMGEN-GCLLSG-CLL9  EUDRACT-2005-003014-15 
Study First Received: January 24, 2006
Last Updated: August 10, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by German CLL Study Group:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine
Fludarabine phosphate
Vidarabine
Darbepoetin alfa
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Hematinics

ClinicalTrials.gov processed this record on August 29, 2016