RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as Campath-1H 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 Campath-1H in treating patients who have chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
stage II chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia stage I chronic lymphocytic leukemia stage III chronic lymphocytic leukemia B-cell Chronic Lymphocytic Leukemia	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Drug: alemtuzumab  Drug: fludarabine	Phase II

Further Study Details: 

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 Campath-1H (monoclonal antibody CD52) consolidation. II. Determine the infectious toxicities of and feasibility of this regimen in this patient population. III. Determine the progression free and overall survival of these patients on this regimen. IV. Determine the immunologic effects of this treatment in these patients.

PROTOCOL OUTLINE: Patients receive fludarabine IV over 30 minutes 5 days a week every 28 days. Treatment continues 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 Campath-1H IV over 2 hours 3 days a week for 6 weeks. Patients undergo clinical staging again after completion of 6 weeks of Campath-1H, followed by 2 more months of observation. Patients are followed every 3 months for the first year, and then every 6 months for the next 8 years.

PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Previously untreated, stage I, II, III, or IV; B-cell chronic lymphocytic leukemia (CLL); Lymphocytosis greater than 5,000/mm3 with less than 55% prolymphocytes; Bone marrow aspirate with greater than 30% of all nucleated cells being lymphoid OR Bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; Overall cellularity must be normocellular or hypercellular; Monoclonal B-cell population positive for at least 1 B-lineage marker (CD19, CD20, CD23, CD24) with coexpression of CD5; Bright surface immunoglobulin levels must have CD23 coexpression
• Stage I or II disease must have evidence of active disease demonstrated by at least 1 of the following: Massive or progressive splenomegaly and/or lymphadenopathy; Presence of weight loss greater than 10% over the preceding 6 month period; Grade 2 or 3 fatigue; Fevers greater than 100.5 degrees Fahrenheit or night sweats for greater than 2 weeks without evidence of infection; Progressive lymphocytosis with an increase of greater than 50% over a 2 month period or an anticipated doubling time of less than 6 months

--Prior/Concurrent Therapy--

• Biologic therapy: No prior biologic therapy for CLL; No concurrent epoetin alfa
• Chemotherapy: No prior chemotherapy for CLL; No other concurrent chemotherapy
• Endocrine therapy: No prior corticosteroids for autoimmune complications that have developed since initial diagnosis of CLL; No concurrent hormones except steroids for new adrenal failure or nondisease related conditions (e.g., insulin for diabetes); No concurrent dexamethasone or other corticosteroid based antiemetics
• Radiotherapy: No concurrent palliative radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Performance status: 0-2
• Life expectancy: Not specified
• Hematopoietic: Direct Coomb's test negative
• Hepatic: Not specified
• Renal: Creatinine no greater than 1.5 times upper limit of normal
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No medical condition requiring chronic oral corticosteroids

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233-1996,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      University of Illinois at Chicago Health Sciences Center, Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Iowa
      Holden Comprehensive Cancer Center at The University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Long Island Jewish Medical Center, New Hyde Park,  New York,  11040,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38103,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Vermont
      CCOP - Southwestern Vermont Regional Cancer Center, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States

Study chairs or principal investigators

Kanti Roop Rai,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000067506; CLB-19901
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004857
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08