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. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effect on the body of combining alemtuzumab with combination chemotherapy and its effectiveness in treating patients who have untreated acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
B-cell adult acute lymphoblastic leukemia L1 adult acute lymphoblastic leukemia L2 adult acute lymphoblastic leukemia T-cell adult acute lymphoblastic leukemia untreated adult acute lymphoblastic leukemia acute undifferentiated leukemia	Drug: alemtuzumab  Drug: asparaginase  Drug: cyclophosphamide  Drug: cytarabine  Drug: daunorubicin  Drug: dexamethasone  Drug: filgrastim  Drug: leucovorin calcium  Drug: mercaptopurine  Drug: methotrexate  Drug: vincristine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the feasibility and toxicity profiles of escalating doses of alemtuzumab during post-remission intensification therapy in patients with untreated acute lymphoblastic leukemia.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the disease-free and overall survival of patients treated with this regimen.
• Determine whether this drug can further reduce minimal residual disease states in these patients.
• Correlate pretreatment characteristics (e.g., cytogenetics and molecular changes) with disease-free and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of alemtuzumab. All courses are 28 days in length except courses 3 and 7 which are 42 days. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Patients receive daunorubicin IV over 5-60 minutes on days 1-3; cyclophosphamide IV over 15-30 minutes on day 1; vincristine IV over 1-2 minutes on days 1, 8, 15, and 22; oral dexamethasone on days 1-7 and 15-21; asparaginase subcutaneously (SC) on days 5, 8, 11, 15, 18, and 22; and filgrastim (G-CSF) SC once daily beginning on day 4 and continuing until blood counts recover.* NOTE: *Patients 60 years of age and over do not receive cyclophosphamide and receive dexamethasone on days 1-7 only.
• Course 2 (early intensification): After sufficient recovery from course 1, patients receive cyclophosphamide IV over 15-30 minutes on day 1; cytarabine IV over 3 hours on days 1-3; methotrexate intrathecally (IT) on day 1; asparaginase SC on days 15, 18, and 22; and G-CSF once daily beginning on day 4 and continuing until blood counts recover.
• After sufficient recovery from course 2, patients receive vincristine IV over 1-2 minutes, methotrexate IV over 3 hours, and methotrexate IT on days 1, 15, and 29; oral methotrexate every 6 hours for 4 doses beginning 6 hours after the start of methotrexate IV infusion on days 1, 15, and 29; oral mercaptopurine on days 1-35; leucovorin calcium IV over 5-10 minutes on days 2, 16, and 30; and oral leucovorin calcium every 6 hours for 8 doses beginning 12 hours after IV leucovorin calcium on days 3 and 4, 17 and 18, and 31 and 32. Patients who have CD52^+ disease as determined by pretreatment immunohistochemistry, and meet all of the following criteria proceed to course 4.
• M_0 or M_1 marrow with absolute neutrophil count at least 1,500/mm^3 and platelet count at least 100,000/mm^3
• AST less than 3 times upper limit of normal
• Cytomegalovirus polymerase chain reaction negative
• No serious infection All other patients proceed to course 5.
• Patients receive alemtuzumab SC 3 times per week for 4 weeks. Cohorts of at least 6 patients receive escalating doses of alemtuzumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 6 or 5 of 12 patients experience dose-limiting toxicity.
• Phase II: Patients receive treatment as in phase I at the MTD of alemtuzumab.
• Course 5 (late intensification): Beginning 2-6 weeks after the completion of course 4, patients receive treatment as in course 1 except with dexamethasone on days 1-7 only.
• Course 6 (late intensification): After sufficient recovery from course 5, patients receive treatment as in course 2.
• Course 7 (CNS intensification): After sufficicient recovery from course 6, patients receive treatment as in course 3.
• : After completion of courses 1-7 and in the absence of disease progression, patients receive maintenance therapy. Patients receive oral mercaptopurine daily; vincristine IV over 1-2 minutes on day 1; oral methotrexate once weekly on days 1, 8, 15, and 22; and oral dexamethasone on days 1-5. Courses repeat every 28 days for up to 24 months from study entry. For testicular disease at study entry that persists or worsens after 4 weeks of therapy or testicular disease that develops after study therapy has begun, patients undergo testicular radiotherapy once daily 5 days a week for 13 treatments.

Patients with CNS leukemia receive methotrexate IT 1-2 times weekly for 5 weeks and leucovorin calcium IV 24 hours after each methotrexate dose. Patients also undergo cranial radiotherapy once daily 5 days a week for 12 treatments. Radiotherapy begins on day 5 of course 1 for patients with CNS leukemia at study entry or the day after diagnosis of CNS leukemia for patients who develop disease after study therapy has begun. If remission is achieved, patients continue study therapy and receive methotrexate once monthly for 12 months.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years from study entry.

PROJECTED ACCRUAL: A total of 18-36 patients will be accrued for phase I within 5-12 months. A total of 14-35 patients will be accrued for phase II within 4-10 months.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed precursor B- or T-lymphoblastic leukemia, L1 or L2 acute lymphoblastic leukemia (ALL), or acute undifferentiated leukemia
• No Burkitt-type ALL
• No prior treatment for leukemia except for any of the following:
• Emergency leukapheresis
• Emergency treatment for hyperleukocytosis with hydroxyurea
• Cranial radiotherapy for CNS leukostasis (1 dose only)
• Must have a pretreatment bone marrow or peripheral blood sample submitted for central immunophenotyping
• Only patients who express CD52 at least 10% in the leukemic blast cell channel are eligible to receive alemtuzumab during module D, course IV
• Must be entered on CLB 9665, 9862, and 8461

PATIENT CHARACTERISTICS: Age

• 15 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• No nursing for at least 3 months after study therapy
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No concurrent palliative radiotherapy
• Concurrent whole brain radiotherapy allowed for documented CNS disease

Surgery

• Not specified

Other

• No concurrent alcoholic beverages
• No concurrent over-the-counter pain relievers

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Palm Beach Cancer Institute - West Palm Beach, West Palm Beach,  Florida,  33401,  United States; Recruiting
Illinois
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States; Recruiting
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States; Recruiting
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting

Study chairs or principal investigators

Wendy Stock, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000302482; CALGB-10102; NCT00061945
Record last reviewed:  July 2004
Last Updated:  March 28, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00061945
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08