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

May 9, 2018 updated by: German CLL Study Group

Darbepoetin Alfa in Patients With Chronic Lymphocytic Leukemia and Comorbidity

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

97

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 subcutaneously 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 subcutaneously 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 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: up to 24 months after the last dose of study medication
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 2 months after the end of the last cycle
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
toxicity
Time Frame: 28 days after the end of the last cycle
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2004

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

January 24, 2006

First Submitted That Met QC Criteria

January 24, 2006

First Posted (Estimate)

January 25, 2006

Study Record Updates

Last Update Posted (Actual)

May 11, 2018

Last Update Submitted That Met QC Criteria

May 9, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL9
  • GCLLSG-CLL9
  • EU-20561
  • AMGEN-GCLLSG-CLL9
  • 2005-003014-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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