Back to resultsCyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
filgrastim
carmustine
cyclophosphamide
cytarabine
dexamethasone
etoposide
fludarabine phosphate
melphalan
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring 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, refractory chronic lymphocytic leukemia
Eligibility Criteria
DISEASE CHARACTERISTICS: Patients with chronic lymphocytic leukemia, meeting 1 of the following criteria: Binet stage B or C disease Binet stage A disease and at high risk for disease progression, defined as the following: Non-nodular marrow infiltration or lymphocyte doubling time < 12 months Thymidine kinase > 7.0 U/L or ß-2-microglobulin > 3.5 mg/L Polymerase chain reaction-amplifiable clonal CDRIII rearrangement of the IgV_H PATIENT CHARACTERISTICS: ECOG performance status 0-1 No concurrent disease resulting in major organ dysfunction PRIOR CONCURRENT THERAPY: No prior combination therapy comprising melphalan, dexamethasone, carmustine, cytarabine, and etoposide (DEXA-Beam) No more than 1 prior chemotherapy regimen No prior chemotherapy regimen longer than 6 months in duration
Sites / Locations
- Hanuschkrankenhaus
- Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
- Humaine - Clinic
- Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
- Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
- Universitaetsklinikum Bonn
- Praxis Dres. F.& G. Doering
- Universitatsklinikum Carl Gustav Carus
- Universitaetsklinikum Duesseldorf
- Michael Schaefers und Partner
- Onkologische Schwerpunkt Praxis
- Universitaetsklinikum Essen
- Malteser Krankenhaus
- Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
- Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
- Universitätsklinikum Göttingen
- Asklepios Klinik St. Georg
- St. Marien-Hospital Hamm - Klinik Knappenstrasse
- Krankenhaus Siloah - Medizinische Klinik II
- Medizinische Hochschule Hannover
- Universitaets-Kinderklinik Heidelberg
- Universitatsklinikum Heidelberg
- Universitaetsklinikum des Saarlandes
- Klinikum der Friedrich-Schiller Universitaet Jena
- Westpfalz-Klinikum GmbH
- Gemeinschaftspraxis fuer Haematologie, Onkologie und Infektiologie
- Internistische Gemeinschaftspraxis - Kassel
- Staedtisches Krankenhaus Kiel
- University Leipzig Clinic of Internal Medicine
- Universitaets - Kinderklinik - Luebeck
- Sana Kliniken Luebeck
- Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
- Universitatsklinik Mainz
- Krankenhaus Maria Hilf GmbH
- University of Muenster
- Klinikum der Universitaet Muenchen - Innenstadt Campus
- Krankenhaus Muenchen Schwabing
- Klinikum der Universitaet Muenchen - Grosshadern Campus
- Staedtisches Krankenhaus Muenchen - Harlaching
- Internistische Praxis - Neuss
- Praxis fuer Haematologie und Interne Onkologie
- Klinikum Nuernberg - Klinikum Nord
- Internistische Gemeinschaftspraxis - Oldenburg
- Klinikum Oldenburg
- Klinikum Ernst Von Bergmann
- Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
- Diakonie Klinikum Stuttgart
- Buergerhospital Stuttgart
- Internistische Praxis - Trier
- Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
- Deutsche Klinik fuer Diagnostik
- Hamatologisch - Onkologische Praxis Wurzburg
- University Wurzburg
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
High dose therapy + autologous PBSCT
Arm Description
Cytoreductive treatment: (preferentially) FC (2-4 cycles) Mobilization: Dexa-BEAM + G-CSF (1-2 cycles) Myeloablation: fractionated TBI (e.g. 6x2Gy) + Cyclophosphamide (2 x 60 mg/kg; d -4 to -3) autologous peripheral blood stem cell transplantation (PBSCT) (d 0)
Outcomes
Primary Outcome Measures
Safety of autologous peripheral stem cell transplantation (PBSCT) as measured by a treatment-related mortality of < 5% at 12 months following transplant
Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant
Secondary Outcome Measures
Safety of mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) as measured by a treatment-related mortality of < 5% before transplant phase
Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest
Complete clinical remissions by NIH criteria at 3 months following transplant
Molecular remissions by CDR3 PCR at 3 months following transplant
Progression-free survival by NIH criteria at 5 years from study entry
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00275015
Brief Title
Cyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia
Official Title
Pivotal Study for High Dose Therapy and Autologous Stem Cell Transplantation in Early Stages of CLL
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
January 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2012 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
German CLL Study Group
4. Oversight
5. Study Description
Brief Summary
RATIONALE: Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an peripheral stem cell transplant for chronic lymphocytic leukemia.
Detailed Description
OBJECTIVES:
Primary
Determine the safety and feasibility of autologous peripheral blood stem cell transplantation in patients with chronic lymphocytic leukemia treated with cyclophosphamide and total-body irradiation.
Secondary
Determine the safety, feasibility, and efficacy of combination therapy comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) and filgrastim (G-CSF) mobilization in patients treated with this regimen.
Determine the efficacy of ex-vivo graft purging in patients treated with this regimen.
Determine the incidence of complete clinical and molecular remissions in patients treated with this regimen.
Determine the progression-free survival of patients treated with this regimen.
OUTLINE: This is a multicenter, open-label, nonrandomized study.
Cytoreductive treatment: Patients undergo 2-4 courses of cytoreductive treatment, preferably following the fludarabine and cyclophosphamide (FC) protocol.
Stem cell mobilization: Patients achieving a complete remission (CR) or partial remission (PR) and stable blood counts undergo stem cell mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, melphalan (Dexa-BEAM), and filgrastim (G-CSF). Patients with an adequate number of mobilized cells undergo stem cell collection. Patients with CR or very good PR proceed to myeloablative therapy.
Myeloablative therapy: Patients undergo total-body irradiation on day -4 and receive cyclophosphamide IV on days -4 and -3.
Autologous peripheral blood stem cell transplantation (PBSCT): Patients undergo autologous PBSCT on day 0.
After completion of study, patients are followed periodically.
PROJECTED ACCRUAL: A total of 150 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
Keywords
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, refractory chronic lymphocytic leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
169 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High dose therapy + autologous PBSCT
Arm Type
Experimental
Arm Description
Cytoreductive treatment: (preferentially) FC (2-4 cycles)
Mobilization: Dexa-BEAM + G-CSF (1-2 cycles)
Myeloablation:
fractionated TBI (e.g. 6x2Gy) + Cyclophosphamide (2 x 60 mg/kg; d -4 to -3)
autologous peripheral blood stem cell transplantation (PBSCT) (d 0)
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
carmustine
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
bone marrow ablation with stem cell support
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Safety of autologous peripheral stem cell transplantation (PBSCT) as measured by a treatment-related mortality of < 5% at 12 months following transplant
Title
Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant
Secondary Outcome Measure Information:
Title
Safety of mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) as measured by a treatment-related mortality of < 5% before transplant phase
Title
Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest
Title
Complete clinical remissions by NIH criteria at 3 months following transplant
Title
Molecular remissions by CDR3 PCR at 3 months following transplant
Title
Progression-free survival by NIH criteria at 5 years from study entry
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Patients with chronic lymphocytic leukemia, meeting 1 of the following criteria:
Binet stage B or C disease
Binet stage A disease and at high risk for disease progression, defined as the following:
Non-nodular marrow infiltration or lymphocyte doubling time < 12 months
Thymidine kinase > 7.0 U/L or ß-2-microglobulin > 3.5 mg/L
Polymerase chain reaction-amplifiable clonal CDRIII rearrangement of the IgV_H
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
No concurrent disease resulting in major organ dysfunction
PRIOR CONCURRENT THERAPY:
No prior combination therapy comprising melphalan, dexamethasone, carmustine, cytarabine, and etoposide (DEXA-Beam)
No more than 1 prior chemotherapy regimen
No prior chemotherapy regimen longer than 6 months in duration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Dreger
Organizational Affiliation
Universitaets-Kinderklinik Heidelberg
Official's Role
Study Chair
Facility Information:
Facility Name
Hanuschkrankenhaus
City
Vienna
ZIP/Postal Code
A-1140
Country
Austria
Facility Name
Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Humaine - Clinic
City
Bad Saarow
ZIP/Postal Code
D-15526
Country
Germany
Facility Name
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
D-12200
Country
Germany
Facility Name
Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
City
Berlin
ZIP/Postal Code
D-13122
Country
Germany
Facility Name
Universitaetsklinikum Bonn
City
Bonn
ZIP/Postal Code
D-53105
Country
Germany
Facility Name
Praxis Dres. F.& G. Doering
City
Bremen
ZIP/Postal Code
D-28205
Country
Germany
Facility Name
Universitatsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Universitaetsklinikum Duesseldorf
City
Duesseldorf
ZIP/Postal Code
D-40225
Country
Germany
Facility Name
Michael Schaefers und Partner
City
Duisburg
ZIP/Postal Code
D-47051
Country
Germany
Facility Name
Onkologische Schwerpunkt Praxis
City
Erlangen
ZIP/Postal Code
D-91052
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
D-45122
Country
Germany
Facility Name
Malteser Krankenhaus
City
Flensburg
ZIP/Postal Code
D-24939
Country
Germany
Facility Name
Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
City
Giessen
ZIP/Postal Code
D-35392
Country
Germany
Facility Name
Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
City
Greifswald
ZIP/Postal Code
D-17487
Country
Germany
Facility Name
Universitätsklinikum Göttingen
City
Göttingen
ZIP/Postal Code
D-37075
Country
Germany
Facility Name
Asklepios Klinik St. Georg
City
Hamburg
ZIP/Postal Code
D-20099
Country
Germany
Facility Name
St. Marien-Hospital Hamm - Klinik Knappenstrasse
City
Hamm
ZIP/Postal Code
D-59071
Country
Germany
Facility Name
Krankenhaus Siloah - Medizinische Klinik II
City
Hannover
ZIP/Postal Code
D-30449
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
D-30625
Country
Germany
Facility Name
Universitaets-Kinderklinik Heidelberg
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany
Facility Name
Universitatsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany
Facility Name
Universitaetsklinikum des Saarlandes
City
Homburg
ZIP/Postal Code
D-66421
Country
Germany
Facility Name
Klinikum der Friedrich-Schiller Universitaet Jena
City
Jena
ZIP/Postal Code
D-07740
Country
Germany
Facility Name
Westpfalz-Klinikum GmbH
City
Kaiserslautern
ZIP/Postal Code
D-67653
Country
Germany
Facility Name
Gemeinschaftspraxis fuer Haematologie, Onkologie und Infektiologie
City
Karlsruhe
ZIP/Postal Code
D-76135
Country
Germany
Facility Name
Internistische Gemeinschaftspraxis - Kassel
City
Kassel
ZIP/Postal Code
D-34117
Country
Germany
Facility Name
Staedtisches Krankenhaus Kiel
City
Kiel
ZIP/Postal Code
D-23116
Country
Germany
Facility Name
University Leipzig Clinic of Internal Medicine
City
Leipzig
ZIP/Postal Code
D-04103
Country
Germany
Facility Name
Universitaets - Kinderklinik - Luebeck
City
Lubeck
ZIP/Postal Code
D-23538
Country
Germany
Facility Name
Sana Kliniken Luebeck
City
Luebeck
ZIP/Postal Code
D-23560
Country
Germany
Facility Name
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
City
Magdeburg
ZIP/Postal Code
D-39120
Country
Germany
Facility Name
Universitatsklinik Mainz
City
Mainz
ZIP/Postal Code
D-55101
Country
Germany
Facility Name
Krankenhaus Maria Hilf GmbH
City
Moenchengladbach
ZIP/Postal Code
D-41063
Country
Germany
Facility Name
University of Muenster
City
Muenster
ZIP/Postal Code
D-48129
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen - Innenstadt Campus
City
Munich
ZIP/Postal Code
D-80331
Country
Germany
Facility Name
Krankenhaus Muenchen Schwabing
City
Munich
ZIP/Postal Code
D-80804
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen - Grosshadern Campus
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Staedtisches Krankenhaus Muenchen - Harlaching
City
Munich
ZIP/Postal Code
D-81545
Country
Germany
Facility Name
Internistische Praxis - Neuss
City
Neuss
ZIP/Postal Code
D-41460
Country
Germany
Facility Name
Praxis fuer Haematologie und Interne Onkologie
City
Norderstedt
ZIP/Postal Code
D-22844
Country
Germany
Facility Name
Klinikum Nuernberg - Klinikum Nord
City
Nuernberg
ZIP/Postal Code
D-90419
Country
Germany
Facility Name
Internistische Gemeinschaftspraxis - Oldenburg
City
Oldenburg
ZIP/Postal Code
D-26121
Country
Germany
Facility Name
Klinikum Oldenburg
City
Oldenburg
ZIP/Postal Code
D-26133
Country
Germany
Facility Name
Klinikum Ernst Von Bergmann
City
Potsdam
ZIP/Postal Code
D-14467
Country
Germany
Facility Name
Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
City
Rostock
ZIP/Postal Code
D-18057
Country
Germany
Facility Name
Diakonie Klinikum Stuttgart
City
Stuttgart
ZIP/Postal Code
D-70176
Country
Germany
Facility Name
Buergerhospital Stuttgart
City
Stuttgart
ZIP/Postal Code
D-70191
Country
Germany
Facility Name
Internistische Praxis - Trier
City
Trier
ZIP/Postal Code
D-54290
Country
Germany
Facility Name
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
D-89081
Country
Germany
Facility Name
Deutsche Klinik fuer Diagnostik
City
Wiesbaden
ZIP/Postal Code
D-65191
Country
Germany
Facility Name
Hamatologisch - Onkologische Praxis Wurzburg
City
Wurzburg
ZIP/Postal Code
D-97070
Country
Germany
Facility Name
University Wurzburg
City
Wurzburg
ZIP/Postal Code
D-97070
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
22490331
Citation
Dreger P, Dohner H, McClanahan F, Busch R, Ritgen M, Greinix H, Fink AM, Knauf W, Stadler M, Pfreundschuh M, Duhrsen U, Brittinger G, Hensel M, Schetelig J, Winkler D, Buhler A, Kneba M, Schmitz N, Hallek M, Stilgenbauer S; German CLL Study Group. Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial. Blood. 2012 May 24;119(21):4851-9. doi: 10.1182/blood-2011-09-378505. Epub 2012 Apr 5.
Results Reference
result
Links:
URL
http://www.dcllsg.de/en/trial/cll3/index.php
Description
Click here for more information about this study: CLL3 (German CLL Study Group)
Learn more about this trial
Cyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia
We'll reach out to this number within 24 hrs