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

May 9, 2018 updated by: German CLL Study Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

169

Phase

  • Phase 2

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

  • Austria
      • Vienna, Austria, A-1140
        • Hanuschkrankenhaus
      • Wien, Austria, A-1090
        • Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik
  • Germany
      • Bad Saarow, Germany, D-15526
        • Humaine - Clinic
      • Berlin, Germany, D-12200
        • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
      • Berlin, Germany, D-13122
        • Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
      • Bonn, Germany, D-53105
        • Universitaetsklinikum Bonn
      • Bremen, Germany, D-28205
        • Praxis Dres. F.& G. Doering
      • Dresden, Germany, D-01307
        • Universitätsklinikum Carl Gustav Carus
      • Duesseldorf, Germany, D-40225
        • Universitaetsklinikum Duesseldorf
      • Duisburg, Germany, D-47051
        • Michael Schaefers und Partner
      • Erlangen, Germany, D-91052
        • Onkologische Schwerpunkt Praxis
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Flensburg, Germany, D-24939
        • Malteser Krankenhaus
      • Giessen, Germany, D-35392
        • Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie
      • Greifswald, Germany, D-17487
        • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
      • Göttingen, Germany, D-37075
        • Universitätsklinikum Göttingen
      • Hamburg, Germany, D-20099
        • Asklepios Klinik St. Georg
      • Hamm, Germany, D-59071
        • St. Marien-Hospital Hamm - Klinik Knappenstrasse
      • Hannover, Germany, D-30625
        • Medizinische Hochschule Hannover
      • Hannover, Germany, D-30449
        • Krankenhaus Siloah - Medizinische Klinik II
      • Heidelberg, Germany, D-69120
        • Universitaets-Kinderklinik Heidelberg
      • Heidelberg, Germany, D-69120
        • Universitätsklinikum Heidelberg
      • Homburg, Germany, D-66421
        • Universitaetsklinikum des Saarlandes
      • Jena, Germany, D-07740
        • Klinikum der Friedrich-Schiller Universitaet Jena
      • Kaiserslautern, Germany, D-67653
        • Westpfalz-Klinikum GmbH
      • Karlsruhe, Germany, D-76135
        • Gemeinschaftspraxis fuer Haematologie, Onkologie und Infektiologie
      • Kassel, Germany, D-34117
        • Internistische Gemeinschaftspraxis - Kassel
      • Kiel, Germany, D-23116
        • Staedtisches Krankenhaus Kiel
      • Leipzig, Germany, D-04103
        • University Leipzig Clinic of Internal Medicine
      • Lubeck, Germany, D-23538
        • Universitaets - Kinderklinik - Luebeck
      • Luebeck, Germany, D-23560
        • Sana Kliniken Luebeck
      • Magdeburg, Germany, D-39120
        • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
      • Mainz, Germany, D-55101
        • Universitatsklinik Mainz
      • Moenchengladbach, Germany, D-41063
        • Krankenhaus Maria Hilf GmbH
      • Muenster, Germany, D-48129
        • University of Muenster
      • Munich, Germany, D-81377
        • Klinikum der Universitaet Muenchen - Grosshadern Campus
      • Munich, Germany, D-81545
        • Staedtisches Krankenhaus Muenchen - Harlaching
      • Munich, Germany, D-80804
        • Krankenhaus Muenchen Schwabing
      • Munich, Germany, D-80331
        • Klinikum der Universitaet Muenchen - Innenstadt Campus
      • Neuss, Germany, D-41460
        • Internistische Praxis - Neuss
      • Norderstedt, Germany, D-22844
        • Praxis fuer Haematologie und Interne Onkologie
      • Nuernberg, Germany, D-90419
        • Klinikum Nuernberg - Klinikum Nord
      • Oldenburg, Germany, D-26133
        • Klinikum Oldenburg
      • Oldenburg, Germany, D-26121
        • Internistische Gemeinschaftspraxis - Oldenburg
      • Potsdam, Germany, D-14467
        • Klinikum Ernst von Bergmann
      • Rostock, Germany, D-18057
        • Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock
      • Stuttgart, Germany, D-70176
        • Diakonie Klinikum Stuttgart
      • Stuttgart, Germany, D-70191
        • Buergerhospital Stuttgart
      • Trier, Germany, D-54290
        • Internistische Praxis - Trier
      • Ulm, Germany, D-89081
        • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
      • Wiesbaden, Germany, D-65191
        • Deutsche Klinik fuer Diagnostik
      • Wurzburg, Germany, D-97070
        • University Würzburg
      • Wurzburg, Germany, D-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

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: cyclophosphamide
Radiation: radiation therapy
Drug: cytarabine
Drug: dexamethasone
Drug: etoposide
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
Biological: filgrastim
Drug: melphalan
Drug: carmustine
Procedure: bone marrow ablation with stem cell support

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome 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
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

Collaborators and Investigators

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

Sponsor

German CLL Study Group

Investigators

  • Study Chair: Peter Dreger, Universitaets-Kinderklinik Heidelberg

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

January 1, 1998

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

January 10, 2006

First Submitted That Met QC Criteria

January 10, 2006

First Posted (Estimate)

January 11, 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

  • CLL3
  • EU-20553

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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