RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of flavopiridol in treating children who have relapsed or refractory solid tumors or lymphoma.

Condition	Treatment or Intervention	Phase
childhood bone cancer childhood brain cancer childhood eye cancer childhood kidney tumors childhood non-Hodgkin's lymphoma childhood soft tissue sarcoma	Drug: flavopiridol  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of flavopiridol in children with relapsed or refractory solid tumors or lymphomas.
• Determine the toxic effects and pharmacokinetics of this drug in these patients.
• Determine the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 18 months.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed relapsed or refractory solid tumor or lymphoma including:
• Neuroblastoma
• Osteosarcoma
• Ewing's sarcoma
• Rhabdomyosarcoma
• Wilms tumor
• CNS tumors
• Histological verification not required for brainstem tumors
• No acute leukemia
• Not eligible for higher priority COG phase I/II study

PATIENT CHARACTERISTICS:

Age:

• Under 22

Performance status:

• Karnofsky 50-100% (over age 10)
• Lansky 50-100% (age 10 and under)

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3 (transfusion independent)
• Hemoglobin at least 8.0 g/dL (transfusion allowed)
• No granulocytopenia, anemia, and/or thrombocytopenia due to bone marrow involvement

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGPT no greater than 5 times normal
• Albumin at least 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal

Cardiovascular:

• Shortening fraction at least 27% by echocardiogram OR
• Ejection fraction at least 50% by MUGA

Other:

• Stable neurologic deficits within the past 2 weeks for patients with CNS tumors
• CNS toxicity less than grade 2
• No active graft-versus-host disease
• No active uncontrolled infection or other serious medical condition
• No uncontrolled diabetes mellitus
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 7 days since prior biologic therapy and recovered
• Prior bone marrow or stem cell transplantation allowed
• At least 6 months since prior allogeneic stem cell transplantation
• At least 1 week since prior growth factors
• No concurrent immunomodulating agents

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent dexamethasone for CNS tumors allowed if on stable dose for at least 2 weeks prior to study
• Concurrent corticosteroids allowed only for increased intracranial pressure in patients with CNS tumors

Radiotherapy:

• At least 2 weeks since prior local (small port) palliative radiotherapy
• At least 6 months since prior radiotherapy to 50% or more of the pelvis
• At least 6 months since prior craniospinal radiotherapy
• At least 6 weeks since other prior substantial bone marrow radiotherapy
• Recovered from prior radiotherapy
• No concurrent radiotherapy except localized palliative radiotherapy

Surgery:

• Not specified

Other:

• No concurrent anticonvulsants

Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Jonathan Jaques Children's Cancer Center, Long Beach,  California,  90801-1428,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143-0128,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218-1088,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Florida
      Shands Hospital and Clinics, University of Florida, Gainesville,  Florida,  32610-100277,  United States
Georgia
      Emory University Hospital - Atlanta, Atlanta,  Georgia,  30322,  United States
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Floating Hospital for Children, Boston,  Massachusetts,  02111,  United States
Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States
      Mott Children's Hospital, Ann Arbor,  Michigan,  48109-0914,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      Columbia Presbyterian Hospital, New York,  New York,  10032,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021-4885,  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
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      Saint Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0361,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Virginia
      Children's Hospital of the King's Daughters, Norfolk,  Virginia,  23507,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
      Madigan Army Medical Center, Tacoma,  Washington,  98431-5000,  United States
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Hospital and Clinics, Madison,  Wisconsin,  53792-0001,  United States
Australia, South Australia
      Women's and Children's Hospital, North Adelaide,  South Australia,  5006,  Australia
Australia, Victoria
      Royal Children's Hospital, Parkville,  Victoria,  3052,  Australia
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada

Study chairs or principal investigators

James A. Whitlock, MD,  Study Chair,  Vanderbilt-Ingram Cancer Center   

Study ID Numbers:  CDR0000068491; COG-ADVL0017; CCG-AO972; NCI-A0972
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012181
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08