Cyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Pivotal Study for High Dose Therapy and Autologous Stem Cell Transplantation in Early Stages of CLL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00275015
• Other study ID #: CLL3
• Secondary ID: EU-20553
• Status: Completed
• Phase: Phase 2
• Start date: January 1998
• Est. completion date: April 2012

Study information

• Verified date: May 2018
• Source: German CLL Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 169
• Est. completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• filgrastim

Drug:
• carmustine

• cyclophosphamide

• cytarabine

• dexamethasone

• etoposide

• fludarabine phosphate

• melphalan

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Hanuschkrankenhaus	Vienna
Austria	Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik	Wien
Germany	Humaine - Clinic	Bad Saarow
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Praxis Dres. F.& G. Doering	Bremen
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Michael Schaefers und Partner	Duisburg
Germany	Onkologische Schwerpunkt Praxis	Erlangen
Germany	Universitaetsklinikum Essen	Essen
Germany	Malteser Krankenhaus	Flensburg
Germany	Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie	Giessen
Germany	Universitätsklinikum Göttingen	Göttingen
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	St. Marien-Hospital Hamm - Klinik Knappenstrasse	Hamm
Germany	Krankenhaus Siloah - Medizinische Klinik II	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaets-Kinderklinik Heidelberg	Heidelberg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Klinikum der Friedrich-Schiller Universitaet Jena	Jena
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Gemeinschaftspraxis fuer Haematologie, Onkologie und Infektiologie	Karlsruhe
Germany	Internistische Gemeinschaftspraxis - Kassel	Kassel
Germany	Staedtisches Krankenhaus Kiel	Kiel
Germany	University Leipzig Clinic of Internal Medicine	Leipzig
Germany	Universitaets - Kinderklinik - Luebeck	Lubeck
Germany	Sana Kliniken Luebeck	Luebeck
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	Universitatsklinik Mainz	Mainz
Germany	Krankenhaus Maria Hilf GmbH	Moenchengladbach
Germany	University of Muenster	Muenster
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum der Universitaet Muenchen - Innenstadt Campus	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Staedtisches Krankenhaus Muenchen - Harlaching	Munich
Germany	Internistische Praxis - Neuss	Neuss
Germany	Praxis fuer Haematologie und Interne Onkologie	Norderstedt
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Internistische Gemeinschaftspraxis - Oldenburg	Oldenburg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Klinikum Ernst Von Bergmann	Potsdam
Germany	Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock	Rostock
Germany	Buergerhospital Stuttgart	Stuttgart
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Internistische Praxis - Trier	Trier
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	Deutsche Klinik fuer Diagnostik	Wiesbaden
Germany	Hamatologisch - Onkologische Praxis Wurzburg	Wurzburg
Germany	University Wurzburg	Wurzburg

Sponsors (1)

Lead Sponsor	Collaborator
German CLL Study Group

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (1)

Dreger P, Döhner H, McClanahan F, Busch R, Ritgen M, Greinix H, Fink AM, Knauf W, Stadler M, Pfreundschuh M, Dührsen U, Brittinger G, Hensel M, Schetelig J, Winkler D, Bühler A, Kneba M, Schmitz N, Hallek M, Stilgenbauer S; German CLL Study Group. Early a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of autologous peripheral stem cell transplantation (PBSCT) as measured by a treatment-related mortality of < 5% at 12 months following transplant
Primary	Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant
Secondary	Safety of mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) as measured by a treatment-related mortality of < 5% before transplant phase
Secondary	Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest
Secondary	Complete clinical remissions by NIH criteria at 3 months following transplant
Secondary	Molecular remissions by CDR3 PCR at 3 months following transplant
Secondary	Progression-free survival by NIH criteria at 5 years from study entry

External Links

•   Click here for more information about this study: CLL3 (German CLL Study Group)