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 506U78 in treating patients who have hematologic cancer and kidney or liver impairment.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma	Procedure: chemotherapy  Drug: U78	Phase I

OBJECTIVES: I. Determine the maximum tolerated dose of 506U78 in patients with hematologic malignancies and renal or hepatic impairment. II. Establish dosing guidelines for this drug in this patient population. III. Determine the toxicities and pharmacokinetics of this drug in these patients.

PROTOCOL OUTLINE: Patients are stratified into 5 groups according to renal and hepatic function: Group 1: Normal renal function and normal hepatic function Group 2: Moderate renal impairment and normal hepatic function Group 3: Severe renal impairment and normal hepatic function Group 4: End stage renal impairment and normal hepatic function Group 5: Normal renal function and moderate hepatic impairment Group 1: Patients receive 506U78 IV over 2 hours on days 1, 3, and 5. Groups 2-5: Patients receive 506U78 IV over 2 hours on days 1, 3, and 5. Dose escalation occurs independently in each of the treatment groups. Cohorts of 3-6 patients receive escalating doses of 506U78 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 toxicities. Treatment repeats every 4 weeks for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: Approximately 60 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed hematologic malignancy that has failed standard therapy or for which no standard therapy exists, including, but not limited to, the following: Acute lymphocytic leukemia; Acute myelogenous leukemia Chronic lymphocytic leukemia; Chronic myelogenous leukemia; Multiple myeloma; Non-Hodgkin's lymphoma; Hodgkin's disease
• No history of CNS disease, including carcinomatous meningitis

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior immunotherapy (e.g., interferon, monoclonal antibodies); No concurrent interleukin-11 for treatment or prevention of thrombocytopenia; No concurrent prophylactic colony stimulating factors
• Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for melphalan, carmustine, or mitomycin); At least 72 hours since prior hydroxyurea; No prior 506U78; No other concurrent chemotherapy
• Endocrine therapy: At least 72 hours since prior glucocorticoids; Concurrent continuation of steroids for adrenal failure allowed; No concurrent hormones except for nondisease related conditions (e.g., insulin for diabetes); No concurrent dexamethasone or other steroidal antiemetics
• Radiotherapy: At least 4 weeks since prior radiotherapy; No concurrent palliative radiotherapy; No concurrent whole brain irradiation for documented CNS disease
• Surgery: Not specified
• Other: At least 72 hours since prior aspirin

--Patient Characteristics--

• Age: 18 and over
• Performance status: CTC 0-2
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin: Groups 1-4: Less than 1.5 times upper limit of normal (ULN); Group 5: 1.5-4 times ULN
• Renal: Creatinine clearance: Groups 1 and 5: Greater than 50 mL/min; Group 2: 30-50 mL/min Group 3: Less than 30 mL/min; Group 4: Less than 30 mL/min, requiring dialysis
• Neurologic: No history of grade 2 peripheral neuropathy; No history of seizure disorder; No history of neurologic dysfunction
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; HIV negative

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
Iowa
      Holden Comprehensive Cancer Center at The University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States

Study chairs or principal investigators

Todd M. Zimmerman,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000067483; CLB-69803
Record last reviewed:  January 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004239
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-22