Alvocidib in Treating Patients With Metastatic or Unresectable Refractory Solid Tumors or Hematologic Malignancies

Inclusion Criteria:

• Histologically confirmed malignancy, including the following types:

  • Hematologic malignancy, including any of the following: (Accrual for patients with hematologic malignancies temporarily closed as of 11/30/04)
  • Mantle cell lymphoma
  • Morphologically confirmed disease
  • CD20 and CD5 positive
  • Any other refractory lymphoma
  • Chronic lymphocytic leukemia

• Rai stage III or IV and meeting at least 1 of the following criteria for active disease:

  • Weight loss > 10% in the last 6 months
  • Fatigue
  • Fever or night sweats with no evidence of infection
  • Progressive anemia or thrombocytopenia
  • Progressive lymphocytosis with a lymphocyte doubling time of < 6 months
  • Marked hypogammaglobulinemia or paraproteinemia
  • Progressive splenomegaly and/or lymphadenopathy
  • Multiple myeloma
  • Disease confirmed by bone marrow aspirate and/or biopsy
  • Relapsed or refractory disease after the most recent treatment regimen
  • Quantifiable monoclonal immunoglobulin in serum and/or urine

• Solid tumor, including but not limited to any of the following:

  • Breast cancer
  • Histologically or cytologically confirmed stage IV invasive disease
  • HER-2 positivity not required for study enrollment
  • Tumor overexpressing HER-2 should be confirmed by immunohistochemistry OR fluorescence in situ hybridization
  • Small cell lung cancer
  • Extensive stage or limited stage disease in relapse
  • Extrapulmonary small cell carcinoma allowed
  • Squamous cell carcinoma of the head and neck
  • Metastatic, recurrent, or refractory disease
  • Renal cell carcinoma
  • Mesothelioma
  • Pleural or peritoneal disease of epithelial, sarcomatoid, or mixed subtype
  • Melanoma
  • Kaposi's sarcoma
  • Metastatic or unresectable disease for which standard therapy does not exist or is no longer effective
  • Measurable or nonmeasurable disease (solid tumor patients)
  • Measurable disease defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or 10 mm by spiral CT scan

• Nonmeasurable disease includes any of the following:

  • All other lesions, including lesions < 20 mm by conventional techniques or 10 mm by spiral CT scan
  • Bone lesions
  • Cytologically positive pleural or peritoneal disease
  • Elevated tumor marker (e.g., CEA, CA 125, CA 19-9, or other tumor marker)
  • Multinodular or confluent nonmeasurable pulmonary, hepatic, adrenal, intra-abdominal, or skin metastases
  • Previously treated with at least 1 chemotherapy regimen*
  • Prior therapy may have included combined modality treatment (e.g., full-dose chemotherapy and radiotherapy with radiosensitizing chemotherapy)
  • Prior therapy with flavopiridol allowed provided the patient was enrolled in a flavopiridol clinical trial employing a different schedule NOTE: *Except in cases where chemotherapy is not known to be effective (e.g., renal cell carcinoma, chondrosarcoma, or gastrointestinal stromal tumor)
  • No active CNS metastases

• History of CNS metastases allowed provided all of the following criteria are met:

  • Previously treated and stable and asymptomatic for at least 4 weeks since the completion of treatment
  • Image documentation required
  • Off steroids or on a stable dose of steroids for at least 1 week

• Hormone receptor status:

  • Not specified

• Age

  • 18 and over

• Sex

  • Male or female

• Menopausal status

  • Not specified

• Performance status

  • ECOG 0-1 OR
  • Karnofsky 70-100%

• Life expectancy

  • More than 12 weeks

• Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3*
  • Platelet count > 75,000/mm^3 (50,000 for hematologic malignancies)* (Accrual for patients with hematologic malignancies temporarily closed as of 11/30/04) NOTE: *Unless abnormality is caused by tumor burden and not cumulative prior chemotherapy

• Hepatic

  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)

• Renal

  • Creatinine ≤ 2.0 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min

• Cardiovascular

  • No myocardial infarction within the past 6 months
  • No unstable angina within the past 6 months
  • No transient ischemic attack or cerebrovascular accident within the past 6 months
  • No history of arterial vascular events
  • No new cardiac arrhythmias likely to be related to cardiac ischemia within the past 6 months
  • No symptomatic congestive heart failure

• Pulmonary

  • No history of pulmonary embolism within the past 6 months

• Gastrointestinal

  • No chronic diarrheal disease within the past 6 months
  • No severe malnutrition
  • No intractable emesis

• Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective hormonal or barrier contraception
  • No ongoing or active infection
  • No other concurrent uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• At least 3 weeks since prior radiotherapy No prior radiotherapy to 50% or more of bone marrow
• Recovered from all prior therapy No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients