Clinical trial NCT00275015: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
First posted: 2006-01-11
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of autologous peripheral stem cell transplantation (PBSCT) as measured by a treatment-related mortality of < 5% at 12 months following transplant
measure: Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant
Secondary outcomes:
measure: Safety of mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) as measured by a treatment-related mortality of < 5% before transplant phase
measure: Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest
measure: Complete clinical remissions by NIH criteria at 3 months following transplant
measure: Molecular remissions by CDR3 PCR at 3 months following transplant
measure: Progression-free survival by NIH criteria at 5 years from study entry
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Hanuschkrankenhaus
city: Wien
country: Austria
facility: Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
city: Bad Saarow
country: Germany
facility: Humaine - Clinic
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Bremen
country: Germany
facility: Praxis Dres. F.& G. Doering
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Duisburg
country: Germany
facility: Michael Schaefers und Partner
city: Erlangen
country: Germany
facility: Onkologische Schwerpunkt Praxis
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Flensburg
country: Germany
facility: Malteser Krankenhaus
city: Giessen
country: Germany
facility: Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamm
country: Germany
facility: St. Marien-Hospital Hamm - Klinik Knappenstrasse
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitaets-Kinderklinik Heidelberg
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller Universitaet Jena
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Gemeinschaftspraxis fuer Haematologie, Onkologie und Infektiologie
city: Kassel
country: Germany
facility: Internistische Gemeinschaftspraxis - Kassel
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel
city: Leipzig
country: Germany
facility: University Leipzig Clinic of Internal Medicine
city: Lubeck
country: Germany
facility: Universitaets - Kinderklinik - Luebeck
city: Luebeck
country: Germany
facility: Sana Kliniken Luebeck
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mainz
country: Germany
facility: Universitatsklinik Mainz
city: Moenchengladbach
country: Germany
facility: Krankenhaus Maria Hilf GmbH
city: Muenster
country: Germany
facility: University of Muenster
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Innenstadt Campus
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Staedtisches Krankenhaus Muenchen - Harlaching
city: Neuss
country: Germany
facility: Internistische Praxis - Neuss
city: Norderstedt
country: Germany
facility: Praxis fuer Haematologie und Interne Onkologie
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Oldenburg
country: Germany
facility: Internistische Gemeinschaftspraxis - Oldenburg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Potsdam
country: Germany
facility: Klinikum Ernst Von Bergmann
city: Rostock
country: Germany
facility: Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Buergerhospital Stuttgart
city: Trier
country: Germany
facility: Internistische Praxis - Trier
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Wiesbaden
country: Germany
facility: Deutsche Klinik fuer Diagnostik
city: Wurzburg
country: Germany
facility: Hamatologisch - Onkologische Praxis Wurzburg
city: Wurzburg
country: Germany
facility: University Wurzburg
Study officials:
affiliation: Universitaets-Kinderklinik Heidelberg
name: Peter Dreger
role: STUDY_CHAIR
References:
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.