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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Steven E. Coutre, Stanford University
ClinicalTrials.gov Identifier:
NCT00230282
First received: September 28, 2005
Last updated: September 25, 2014
Last verified: September 2014

September 28, 2005
September 25, 2014
July 2004
December 2010   (final data collection date for primary outcome measure)
Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

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
Not Provided
Complete list of historical versions of study NCT00230282 on ClinicalTrials.gov Archive Site
Duration of Response [ Time Frame: 105 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • B-cell Leukemia
  • Chronic Leukemia
  • Chronic Lymphocytic Leukemia (CLL)
  • 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
    • Cytoxan
    • Neosar
    • Procytox
    • Revimmune
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.
Interventions:
  • Drug: Alemtuzumab
  • Drug: Fludarabine
  • Drug: Cytoxan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
October 2011
December 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00230282
IRB-13053, 31185, 80071, HEMCLL0001
Yes
Steven E. Coutre, Stanford University
Steven E. Coutre
Bayer
Principal Investigator: Steven Edward Coutre Stanford University
Stanford University
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP