Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

506U78 in Treating Patients With Hematologic Cancer and Kidney or Liver Impairment

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	CLB-69803 NCT00004239, CALGB-69803

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.

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

Expected Enrollment

Approximately 60 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Todd Zimmerman, MD, Protocol chair		Ph: 773-702-4159; 888-824-0200 Email: tzimmerm@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase I Study of Compound 506U78 (NSC #686673) in Patients with Hematologic Malignancies and Renal or Hepatic Impairment
Trial Start Date		1999-12-15
Registered in ClinicalTrials.gov		NCT00004239
Date Submitted to PDQ		1999-12-22
Information Last Verified		2002-05-01
NCI Grant/Contract Number		U10-CA31946

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