RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have untreated acute lymphoblastic leukemia.

Condition	Treatment or Intervention	Phase
L1 adult acute lymphoblastic leukemia L2 adult acute lymphoblastic leukemia untreated adult acute lymphoblastic leukemia	Drug: asparaginase  Drug: cyclophosphamide  Drug: cytarabine  Drug: daunorubicin  Drug: filgrastim  Drug: leucovorin calcium  Drug: mercaptopurine  Drug: methotrexate  Drug: prednisone  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the complete response rate and toxicity of escalating doses of daunorubicin in patients under 60 years old with untreated acute lymphoblastic leukemia (ALL). II. Determine the complete response rate and toxicity of a constant dose of daunorubicin in patients at least 60 years old with untreated ALL. III. Determine the toxicity of high dose cytarabine during postremission therapy in these patients. IV. Determine the CNS relapse rate of ALL when prophylactic intrathecal methotrexate and high dose intravenous chemotherapy replace cranial irradiation. V. Target a serum methotrexate level of between 1-2uM at 30 hours following initiation of IV methotrexate infusion.

PROTOCOL OUTLINE: Course I: Patients are assigned to 1 of 2 induction treatment groups based on age: Group 1 (under age 60): Patients receive cyclophosphamide IV over 15-30 minutes on day 1, escalating doses of daunorubicin IV over 5-10 minutes on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-21, asparaginase intramuscularly on days 5, 8, 11, 15, 18, and 22, and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 4 and continuing for at least 7 days and then until blood counts recover. Group 2 (age 60 and over): Patients receive vincristine, asparaginase, cyclophosphamide, and G-CSF as in group 1 and fixed dose daunorubicin IV over 5-10 minutes on days 1-3 and oral prednisone on days 1-7. Patients are then evaluated for bone marrow cellularity on day 29. Those with M0, M1, or M2 cellularity proceed to course II. Patients with M3 cellularity may proceed to course II or be removed from study. Course II (early intensification): Patients receive intrathecal methotrexate and cyclophosphamide IV over 15-30 minutes on day 1, cytarabine IV over 3 hours on days 1-3, and G-CSF SQ beginning on day 4. Bone marrow is again examined on day 29. Patients with M0 or M1 cellularity after course I and no sign of relapse after course II proceed to course III. Patients with M2 or M3 cellularity after course I must have M0 or M1 cellularity after course II to proceed to course III. Patients with M2 or M3 cellularity after course II are removed from study. Course III: Patients receive intrathecal methotrexate, vincristine IV, and methotrexate IV over 3 hours on days 1, 8, and 15 and oral methotrexate every 6 hours for 4 doses beginning 6 hours after starting methotrexate IV on days 1, 2, 8, 9, 15, and 16. Patients receive leucovorin calcium IV 6 hours after the last oral methotrexate dose on days 2, 9, and 16 and oral leucovorin calcium beginning 12 hours after leucovorin calcium IV for at least 4 doses on days 3, 4, 10, 11, 17, and 18. Patients who maintain M0 or M1 cellularity on day 29 of course III continue therapy. Those with M2 or M3 cellularity after course III are removed from the study. Course IV (Late intensification): Repeat course I. Course V (Late intensification): Repeat course II. Course VI (CNS intensification): Repeat course III. Course VII (Prolonged maintenance): Patients receive oral mercaptopurine daily, vincristine IV once every 4 weeks, oral prednisone on days 1-5, and oral methotrexate on days 1, 8, 15, and 22. Courses repeat every 4 weeks for up to 18 months. Patients with testicular disease receive gonadal radiotherapy anytime after course I. Chemotherapy is not halted during radiotherapy. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually for 10 years.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study within 15 months.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven acute lymphoblastic leukemia (FAB L1 or L2) or acute undifferentiated leukemia
• Must be registered on companion protocol CALGB-9862

--Prior/Concurrent Therapy--

• Biologic therapy: Prior emergency leukapheresis allowed; No other prior biologic therapy for leukemia
• Chemotherapy: Prior emergency treatment with hydroxyurea for hyperleukocytosis allowed; No other prior chemotherapy for leukemia; No other concurrent chemotherapy
• Endocrine therapy: No prior endocrine therapy for leukemia; No concurrent hormonal therapy (except steroids for adrenal failure or hormones for nondisease related conditions)
• Radiotherapy: One prior dose of cranial radiotherapy for CNS leukostasis allowed; No other prior radiotherapy for leukemia; No concurrent palliative radiotherapy except whole brain irradiation for CNS disease
• Surgery: Not specified

--Patient Characteristics--

• Age: 15 and over
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  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, Georgetown University, 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,  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
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  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
      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,  United States
New Jersey
      Cooper Cancer Institute, Camden,  New Jersey,  08103,  United States
      St. Barnabas Medical Center, Livingston,  New Jersey,  07039,  United States
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  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,  13210,  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 of Wake Forest University Baptist Medical Center, 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,  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
      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

Wendy Stock,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000066807; CLB-19802
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003700
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08