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

Trial Information

A Phase I Study of Compound 506U78 (NSC #686673) in Patients With Hematologic Malignancies and Renal or Hepatic Impairment

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.

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.

Inclusion 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

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

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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

each tx cycle

Safety Issue:

Yes

Principal Investigator

Todd M. Zimmerman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Chicago

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000067483

NCT ID:

NCT00004239

Start Date:

December 1999

Completion Date:

Related Keywords:

Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
stage III multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
polycythemia vera
primary myelofibrosis
essential thrombocythemia
refractory hairy cell leukemia
chronic myelomonocytic leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult T-cell leukemia/lymphoma
previously treated myelodysplastic syndromes
prolymphocytic leukemia
primary systemic amyloidosis
recurrent mantle cell lymphoma
anaplastic large cell lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders

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

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