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
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Stanford University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: 105 months ] [ Designated as safety issue: No ]

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
  • Cytoxan
  • 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: 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

No publications provided

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, 80071, HEMCLL0001
Study First Received: September 28, 2005
Results First Received: August 27, 2014
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
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
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 16, 2014