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Combination Chemotherapy, Total-Body Irradiation, and Alemtuzumab in Treating Patients Undergoing an Autologous Stem Cell Transplant for Stage I, Stage II, Stage III, or Stage IV Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00276809
Recruitment Status : Completed
First Posted : January 13, 2006
Last Update Posted : September 26, 2016
Sponsor:
Information provided by:
German CLL Study Group

Brief Summary:

RATIONALE: Giving combination chemotherapy before a peripheral blood 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. A monoclonal antibody, such as alemtuzumab, is given to kill any remaining cancer cells. Chemotherapy and radiation therapy (total-body irradiation) are 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. Giving combination chemotherapy, total-body irradiation, and alemtuzumab together with autologous peripheral stem cell transplant may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with total-body irradiation and alemtuzumab works in treating patients undergoing an autologous stem cell transplant for stage I, stage II, stage III, or stage IV chronic lymphocytic leukemia.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Biological: alemtuzumab Biological: filgrastim Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: etoposide Drug: fludarabine phosphate Drug: melphalan Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and feasibility of cytoreductive fludarabine and cyclophosphamide followed by high-dose myeloablative therapy comprising total-body irradiation, cyclophosphamide, and alemtuzumab in patients undergoing autologous filgrastim (G-CSF)-mobilized peripheral blood stem cell transplantation for stage I-IV chronic lymphocytic leukemia.

Secondary

  • Determine the clinical and molecular remission rate and duration in patients treated with this regimen.
  • Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, open label, nonrandomized study. Patients are assigned to 1 of 2 cohorts according to time of enrollment.

  • Cytoreductive induction therapy: All patients receive fludarabine IV and cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) or partial response (PR) proceed to stem cell mobilization. Patients with stage III or IV disease at this point are removed from study.
  • Stem cell mobilization: All patients receive Dexa-BEAM comprising oral dexamethasone once daily on days 1-10; carmustine IV and melphalan IV on day 2; and cytarabine IV twice daily and etoposide IV once daily on days 4-7. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 8 and continuing until leukapheresis is completed. Patients undergo peripheral blood stem cell (PBSC) harvest between days 20 and 28. Patients without an adequate number of collected PBSCs may receive a second course of Dexa-BEAM. Patients achieving CR or very good PR proceed to high-dose myeloablative therapy and PBSC transplantation (PBSCT) with or without consolidation therapy.
  • Consolidation therapy: Beginning between 1-2 months after completion of Dexa-BEAM, patients in cohort 2 receive alemtuzumab IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and then proceed to high-dose myeloablative therapy and PBSCT within 1 month after completion of consolidation therapy. Patients in cohort 1 do not receive consolidation therapy and proceed directly to high-dose therapy within 3 months after completion of stem cell mobilization.
  • High-dose myeloablative therapy and PBSCT: Patients undergo total-body irradiation on days -7 to -5. Patients then receive cyclophosphamide IV on days -4 and -3 and alemtuzumab IV over 2 hours on days -10, -9, -8, -6, and -4. Patients undergo PBSCT on day 0.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Campath 1H (Alemtuzumab) Combined With High-Dose Therapy and Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia
Study Start Date : June 2001
Actual Primary Completion Date : September 2004
Actual Study Completion Date : September 2004





Primary Outcome Measures :
  1. Safety and feasibility of CAMPATH-1H included into the myeloablative regimen (cyclophosphamide and TBI) of the CLL3 protocol monitoring of treatment related mortality and morbidity (CTC scale) continuous

Secondary Outcome Measures :
  1. Rate and duration of molecular responses MRD levels continuous
  2. Rate and duration of clinical remissions NCIE sponsored remission criteria for CLL continuous
  3. Overall survival time from treatment to death continuous


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Chronic lymphocytic leukemia (CLL), meeting 1 of the following stage criteria:

    • Stage I-IV disease
    • Binet stage B or C disease
    • Binet stage A disease at high risk for rapid disease progression, as defined by both of the following criteria:

      • Nonnodular marrow infiltration and/or lymphocyte doubling time < 12 months
      • Thymidine kinase > 7.0 U/L and/or ß-2-microglobulin > 3.5 mg/L
  • Polymerase chain reaction-amplifiable clonal CDR III rearrangement of the immunoglobulin variable heavy chain gene
  • No Richter's syndrome or B-prolymphocytic leukemia

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • No concurrent disease resulting in major organ dysfunction
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other concurrent malignancy
  • No New York Heart Association class III or IV cardiac failure
  • No cardiomyopathy
  • No history of myocardial infarction
  • No symptomatic coronary heart disease
  • No severe cardiac arrhythmia
  • No severe or uncontrolled hypertension
  • No chronic pulmonary disease
  • No pulmonary function test impairment
  • No severe or uncontrolled diabetes mellitus
  • Bilirubin or transaminases ≤ 1.5 times upper limit of normal
  • Creatinine ≤ 1.4 mg/dL
  • No cerebral dysfunction
  • No severe psychiatric impairment
  • No drug addiction or alcoholism
  • Negative HIV
  • Negative Hepatitis B or C
  • No allergy to any of the protocol drugs
  • No history of anaphylactic reaction to monoclonal antibodies
  • No active infection

PRIOR CONCURRENT THERAPY:

  • No more than 1 prior chemotherapy regimen OR chemotherapy that lasted > 6 months
  • No prior radiotherapy
  • No prior treatment with alemtuzumab
  • No prior long-term (> 1 month) systemic corticosteroids
  • No prior therapy with dexamethasone, carmustine, etoposide, cytarabine, and melphalan (Dexa-BEAM)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00276809


Locations
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Germany
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, D-12200
Universitaetsklinikum Essen
Essen, Germany, D-45122
Asklepios Klinik St. Georg
Hamburg, Germany, D-20099
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Universitatsklinikum Heidelberg
Heidelberg, Germany, D-69120
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany, 76133
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, Germany, D-24105
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
Universitatsklinik Mainz
Mainz, Germany, 55101
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, Germany, D-81377
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, Germany, D-89081
Sponsors and Collaborators
German CLL Study Group
Investigators
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Study Chair: Stephan Stilgenbauer, MD Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Additional Information:
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ClinicalTrials.gov Identifier: NCT00276809     History of Changes
Other Study ID Numbers: CLL3C
EU-20556
MEDAC-GCLLSG-CLL3C
First Posted: January 13, 2006    Key Record Dates
Last Update Posted: September 26, 2016
Last Verified: September 2016

Keywords provided by German CLL Study Group:
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

Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cytarabine
Dexamethasone
Cyclophosphamide
Fludarabine
Etoposide
Melphalan
Alemtuzumab
Fludarabine phosphate
Carmustine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents