RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PSC 833 may help chemotherapy drugs kill more cancer cells by making them more sensitive to the drugs.

PURPOSE: Phase II trial to study the effectiveness of PSC 833, daunorubicin, and cytarabine in treating older patients who have newly diagnosed acute myeloid leukemia.

Condition	Treatment or Intervention	Phase
untreated adult acute myeloid leukemia adult acute differentiated monocytic leukemia (M5b) adult acute myeloblastic leukemia without maturation (M1) adult acute minimally differentiated myeloid leukemia (M0) adult acute poorly differentiated monocytic leukemia (M5a) adult acute erythroleukemia (M6) adult acute myelomonocytic leukemia (M4) adult acute myeloblastic leukemia with maturation (M2) adult acute megakaryocytic leukemia (M7)	Drug: cytarabine  Drug: daunorubicin  Drug: filgrastim  Drug: PSC 833  Drug: sargramostim	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the safety and efficacy of daunorubicin and cytarabine by continuous infusion and PSC 833 in patients over age 56 with newly diagnosed acute myeloid leukemia.

II. Determine the frequency and severity of toxicities of this regimen in these patients.

III. Determine the frequency and prognosis of functional and phenotypic P-glycoprotein expression, cytogenetics, and pharmacokinetics in this population.

PROTOCOL OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy consisting of PSC 833 IV over 2 hours on day 1, then continuously for 96 hours; daunorubicin IV continuously on days 1-3; and cytarabine IV continuously on days 1-7. Filgrastim (G-CSF) or sargramostim (GM-CSF) is administered subcutaneously (SQ) or IV beginning on day 15 and continuing until blood counts recover or day 21. If patients do not achieve complete remission after one course, a second course is administered.

Patients who achieve A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status after 1 or 2 courses of induction chemotherapy proceed to consolidation therapy, which begins upon recovery from induction therapy. Consolidation therapy consists of PSC 833 over 2 hours on day 1, daunorubicin IV over 1-5 minutes on days 1 and 2, and cytarabine IV continuously on days 1-5. Treatment repeats for a total of 2 courses.

Patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 20-55 patients will be accrued for this study within 8-9 months.

Ages Eligible for Study:  56 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Morphologically confirmed acute myeloid leukemia (AML); No M3 AML or blastic phase chronic myelogenous leukemia
• Must be registered on protocols SWOG-9007 and SWOG-9910

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for acute leukemia; Prior hydroxyurea to control high cell counts allowed; At least 30 days since prior low dose cytarabine (less than 100 mg/m2/day) for myelodysplastic syndrome and recovered; Single dose of prior or concurrent (with induction chemotherapy) intrathecal chemotherapy allowed
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 56 and over
• Performance status: Zubrod 0-3
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN); SGOT/SGPT no greater than 4 times ULN
• Renal: Creatinine no greater than 1.5 times ULN; Creatinine clearance greater than 40 mL/min
• Cardiovascular: LVEF at least 50% by MUGA or echocardiogram; No unstable cardiac arrhythmias or angina
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No other malignancy within the past 5 years except: Adequately treated basal cell or squamous cell skin cancer; Carcinoma in situ of the cervix; Adequately treated stage I or II cancer in complete remission

Alabama
      MBCCOP - University of South Alabama, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      Beckman Research Institute, City of Hope, Los Angeles,  California,  91010,  United States
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
      University of California Davis Medical Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center, Los Angeles,  California,  90033-0800,  United States
      Veterans Affairs Medical Center - Long Beach, Long Beach,  California,  90822,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40511-1093,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Medical Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States
      CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids,  Michigan,  49503,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110-0250,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States
Ohio
      Barrett Cancer Center, The University Hospital, Cincinnati,  Ohio,  45219,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Cleveland Clinic Cancer Center, Cleveland,  Ohio,  44195,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      Texas Tech University Health Science Center, Lubbock,  Texas,  79423,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-1329,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78284,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Vermont
      CCOP - Southwestern Vermont Regional Cancer Center, Bennington,  Vermont,  05201,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Swedish Cancer Institute, Seattle,  Washington,  98104,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States
Canada, British Columbia
      BC Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada

Study chairs or principal investigators

Thomas R. Chauncey,  Study Chair,  Southwest Oncology Group   

Study ID Numbers:  CDR0000067450; SWOG-9918; SWOG-S9918
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004217
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08