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

NCT ID: NCT00275015

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-01-31
• Study Completion Date: 2012-04-30

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High dose therapy + autologous PBSCT

1. Cytoreductive treatment: (preferentially) FC (2-4 cycles)

2. Mobilization: Dexa-BEAM + G-CSF (1-2 cycles)

3. Myeloablation:

fractionated TBI (e.g. 6x2Gy) + Cyclophosphamide (2 x 60 mg/kg; d -4 to -3)

4. autologous peripheral blood stem cell transplantation (PBSCT) (d 0)

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: lead

Principal Investigators

Peter Dreger

Role: STUDY_CHAIR

Universitaets-Kinderklinik Heidelberg

Locations

Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik

Vienna, , Austria

Hanuschkrankenhaus

Vienna, , Austria

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

Michael Schaefers und Partner

Duisburg, , Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, , 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

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , 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

Lübeck, , Germany

Sana Kliniken Luebeck

Lübeck, , Germany

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, , Germany

Universitatsklinik Mainz

Mainz, , Germany

Krankenhaus Maria Hilf GmbH

Mönchengladbach, , Germany

Klinikum der Universitaet Muenchen - Innenstadt Campus

Munich, , Germany

Krankenhaus Muenchen Schwabing

Munich, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Staedtisches Krankenhaus Muenchen - Harlaching

Munich, , Germany

University of Muenster

Münster, , Germany

Internistische Praxis - Neuss

Neuss, , Germany

Praxis fuer Haematologie und Interne Onkologie

Norderstedt, , Germany

Klinikum Nuernberg - Klinikum Nord

Nuremberg, , 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

Diakonie Klinikum Stuttgart

Stuttgart, , Germany

Buergerhospital 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

Würzburg, , Germany

University Wurzburg

Würzburg, , Germany

Countries

Austria; Germany

References

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.

Reference Type: RESULT

PMID: 22490331 (View on PubMed)

Other Identifiers

EU-20553

Identifier Type: -

Identifier Source: secondary_id

CLL3

Identifier Type: -

Identifier Source: org_study_id