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Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00230282
First Posted: September 30, 2005
Last Update Posted: October 6, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Bayer
Information provided by (Responsible Party):
Steven E. Coutre, Stanford University
  Purpose
The primary objective of this study was to evaluate the safety and efficacy of the combination of fludarabine and cyclophosphamide in previously untreated CLL patients. Participants will receive fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles.

Condition Intervention Phase
Leukemia B-cell Leukemia Chronic Leukemia Chronic Lymphocytic Leukemia (CLL) Drug: Alemtuzumab Drug: Fludarabine Drug: Cytoxan Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center Phase 2 Efficacy and Pharmacokinetic Study Evaluating Fludarabine, Cyclophosphamide, and Subcutaneous Campath (FCCam, Alemtuzumab) for Previously Untreated B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Steven E. Coutre, Stanford University:

Primary Outcome Measures:
  • Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR) [ Time Frame: 24 weeks ]

    Response criteria as per the NCI-WG Revised Guidelines for B-CLL

    Complete remission:

    No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes > 1,500/uL, Platelets > 100,000/uL, Hemoglobin > 11.0 g/dL Bone marrow aspirate and biopsy normocellular with < 30% lymphocytes Absent lymphoid nodules

    Partial remission:

    • 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value
    • 50% reduction in lymphadenopathy and/or ≥ 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes > 1,500/uL or 50% improvement over baseline Platelets > 100,000/uL or 50% improvement over baseline Hemoglobin > 11.0 g/dL or 50% improvement over baseline


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: 105 months ]

Enrollment: 25
Study Start Date: July 2004
Study Completion Date: October 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine, cytoxan, then alemtuzumab
Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.
Drug: Alemtuzumab
3 to 30 mg, IV
Other Names:
  • Campath
  • MabCampath
  • Campath-1H
  • Lemtrada
  • FCCam
Drug: Fludarabine
[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Other Name: Fludara
Drug: Cytoxan
(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
Other Names:
  • Cyclophosphamide
  • cytophosphane
  • Endoxan
  • Neosar
  • Procytox
  • Revimmune

Detailed Description:

This single-arm study evaluated the safety and efficacy of the combination of fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC in previously untreated CLL patients. Participants received fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles, followed by a no-treatment rest period (observation) for 3 to 12 weeks.

Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive Campath stating at 3 mg/day with the dose adjusted to the maximum tolerated dose.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ age 18
  • Karnofsky performance status 60% or above
  • Confirmed immunohistological diagnosis of Chronic Lymphocytic Leukemia (CLL)
  • Rai Stage I to IV as follows:

    • Advanced stage disease (Rai Stage III or IV, or modified Rai High Risk)
    • OR
    • Patients with Rai Stage I - II or (Modified Rai Intermediate-Risk) disease must have an indication for therapy based on 1996 NCI revised criteria for active disease as follows:

      • Any one of the following disease-related symptoms:

        1. Weight loss ≥ 10% body weight within the previous 6 months
        2. Extreme fatigue
        3. Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection
        4. Night sweats without evidence of infection
      • Evidence of progressive marrow failure based on the development of worsening of anemia or thrombocytopenia
      • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
      • Massive (> 6 cm below the left costal margin) or progressive splenomegaly
      • Bulky (>10 cm in cluster) or progressive lymphadenopathy
      • Progressive lymphocytosis > 50% increase over 2 months, or anticipated doubling time < 6 months
  • Patients with immunoglobulin VH gene in unmutated nucleotide sequence configuration, as defined by ≥ 98% homology with the nearest germline counterpart
  • Serum creatinine ≤ 2x the upper limit of normal
  • Total serum bilirubin ≤ 2x the upper limit of normal.
  • AST ≤ 2x the upper limit of normal.
  • ALT ≤ 2x the upper limit of normal.
  • Signed written informed consent

Exclusion Criteria:

  • Prior pharmacological treatment for CLL
  • Past history of anaphylaxis following exposure to monoclonal antibodies
  • Active secondary malignancy or a history of malignant disease (other than CLL or non-melanoma skin cancer) within the preceding 5 years
  • Any medical condition requiring systemic corticosteroids
  • Active systemic infection
  • Major systemic or other illness (including Coombs positivity and active hemolysis) that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results
  • HIV positive by serologic testing
  • Pregnant or nursing female
  • Unwilling/unable to practice an acceptable form of contraception.
  Contacts and Locations
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): NCT00230282


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Steven E. Coutre
Bayer
Investigators
Principal Investigator: Steven Edward Coutre Stanford University
  More Information

Responsible Party: Steven E. Coutre, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00230282     History of Changes
Other Study ID Numbers: IRB-13053
31185 ( Other Identifier: Berlex Oncology ID )
80071 ( Other Identifier: Stanford University Alternate IRB Approval Number )
HEMCLL0001 ( Other Identifier: OnCore )
First Submitted: September 28, 2005
First Posted: September 30, 2005
Results First Submitted: August 27, 2014
Results First Posted: September 8, 2014
Last Update Posted: October 6, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Alemtuzumab
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents