Fludarabine Followed by Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00004857
First received: March 7, 2000
Last updated: July 1, 2016
Last verified: July 2016
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as alemtuzumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine followed by alemtuzumab in treating patients who have chronic lymphocytic leukemia.


Condition Intervention Phase
Leukemia
Biological: alemtuzumab
Drug: fludarabine phosphate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Fludarabine Induction Followed by CAMPATH-1H Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Response [ Time Frame: 2 months post consolidation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 2 months post consolidation ] [ Designated as safety issue: Yes ]

Enrollment: 86
Study Start Date: January 2000
Study Completion Date: February 2010
Primary Completion Date: March 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine + Campath-1H
Standard of care induction with fludarabine followed by consolidation antibody therapy
Biological: alemtuzumab
30 mg subQ injection tiw for 6 weeks
Other Name: campath-1H
Drug: fludarabine phosphate
25mg/sq m/day IV infusion x 5 days Wks 1, 5, 9, and 13

Detailed Description:

OBJECTIVES: I. Determine the overall response rate of previously untreated patients with stage I, II, III, or IV B-cell chronic lymphocytic leukemia when treated with fludarabine induction followed by alemtuzumab consolidation. II. Determine the infectious toxic effects and feasibility of this regimen in this patient population. III. Determine the treatment-related toxic effects, including infection and injection site reactions, of subcutaneous vs intravenous alemtuzumab in patients treated with this regimen. IV. Determine the progression-free and overall survival of patients treated with this regimen. V. Determine the immunologic effects of this regimen in these patients.

OUTLINE: Patients receive fludarabine IV over 30 minutes 5 days a week. Treatment repeats every 28 days for 4 courses in the absence of disease progression. Patients undergo clinical staging after completion of course 4 of fludarabine followed by 2 months of observation. Patients with stable or responding disease receive alemtuzumab subcutaneously 3 days a week for 6 weeks. Patients undergo clinical staging again after completion of 6 weeks of alemtuzumab followed by 2 more months of observation. Patients are followed every 3 months for 1 year and then every 6 months for 8 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Specific Diagnosis of B-Cell CLL

    1.1 An absolute lymphocytosis of > 5,000/µl

    1.1.1 Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes.

    1.1.2 Bone marrow examination must include at least a unilateral aspirate and biopsy. The aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL. The overall cellularity must be normocellular or hypercellular.

    1.1.3 Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23, CD24) with the CD5 antigen, in the absence of other pan-T-cell markers. Additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density. Patients with bright surface immunoglobulin levels must have CD23 co-expression.

    1.2 Staging

    1.2.1 Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV) per the protocol.

    1.2.2 Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:

    • Massive or progressive splenomegaly and/or lymphadenopathy
    • Presence of weight loss > 10% over the preceding 6 month period;
    • Grade 2 or 3 fatigue
    • Fevers > 100.5°C or night sweats for greater than 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.
  2. Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.
  3. No medical condition requiring chronic use of oral corticosteroids.
  4. Age ≥18 years.
  5. Performance Status 0 - 2.
  6. No HIV disease. Due to alterations in host immunity, patients with HIV may not be enrolled.
  7. Non-pregnant and non-nursing. Due to the unknown teratogenic potential of Campath-1H, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.
  8. Initial Required Laboratory Values:

Creatinine <1.5 x upper limit of institutional normal value Coomb's Testing NEGATIVE

  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: NCT00004857

  Show 50 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Kanti R. Rai, MD Long Island Jewish Medical Center
  More Information

Publications:
Rai KR, Byrd JC, Peterson B: Subcutaneous alemtuzumab following fludarabine for previously untreated patients with chronic lymphocytic leukemia (CLL): CALGB study 19901. [Abstract] Blood 102 (11 Pt 1): A-2506, 2003.
Rai KR, Byrd JC, Peterson BL, et al.: A phase II trial of fludarabine followed by alemtuzumab (Campath-1H) in previously untreated chronic lymphocytic leukemia (CLL) patients with active disease: Cancer and Leukemia Group B (CALGB) study 19901. [Abstract] Blood 100 (11 Pt 1): A-772, 2002.
Morrison VA, Peterson BL, Rai KR, et al.: Alemtuzumab increases serious infections in patients with previously untreated chronic lymphocytic leukemia (CLL) receiving fludarabine-based therapy: a comparative analysis of 3 Cancer and Leukemia Group B studies (CALGB 9011, 9712, 19901). [Abstract] Blood 110 (11): A-756, 2007.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00004857     History of Changes
Other Study ID Numbers: CALGB-19901  U10CA031946  CDR0000067506 
Study First Received: March 7, 2000
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Additional relevant MeSH terms:
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
Fludarabine
Fludarabine phosphate
Alemtuzumab
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2016