Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00275015
First received: January 10, 2006
Last updated: November 5, 2013
Last verified: April 2007
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: filgrastim
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: etoposide
Drug: fludarabine phosphate
Drug: melphalan
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pivotal Study for High Dose Therapy and Autologous Stem Cell Transplantation in Early Stages of CLL

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: Yes ]
  • Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant [ Designated as safety issue: No ]

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 [ Designated as safety issue: Yes ]
  • Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest [ Designated as safety issue: No ]
  • Complete clinical remissions by NIH criteria at 3 months following transplant [ Designated as safety issue: No ]
  • Molecular remissions by CDR3 PCR at 3 months following transplant [ Designated as safety issue: No ]
  • Progression-free survival by NIH criteria at 5 years from study entry [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: January 1998
Study Completion Date: April 2012
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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275015

  Show 53 Study Locations
Sponsors and Collaborators
German CLL Study Group
Investigators
Study Chair: Peter Dreger Universitaets-Kinderklinik Heidelberg
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00275015     History of Changes
Other Study ID Numbers: CDR0000455090, GCLLSG-CLL3, EU-20553
Study First Received: January 10, 2006
Last Updated: November 5, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Dexamethasone
Fludarabine
Fludarabine phosphate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors

ClinicalTrials.gov processed this record on November 25, 2014