Clinical trial NCT00004239: 506U78 in Treating Patients With Hematologic Cancer and Kidney or Liver Impairment
Official title: A Phase I Study of Compound 506U78 (NSC #686673) in Patients With Hematologic Malignancies and Renal or Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-01-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at The University of Iowa
state: Iowa
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
Study officials:
affiliation: University of Chicago
name: Todd M. Zimmerman, MD
role: STUDY_CHAIR
References: