A Phase I Study of Compound 506U78 (NSC #686673) in Patients With Hematologic Malignancies and Renal or Hepatic Impairment
18 Years
N/A
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
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 |
