Phase I and Pharmacokinetic Study of UCN-01 and Fludarabine in Relapsed or Refractory Low-Grade Lymphoid Malignancies
18 Years
N/A
Both
Leukemia, Lymphoma
Trial Information
Phase I and Pharmacokinetic Study of UCN-01 and Fludarabine in Relapsed or Refractory Low-Grade Lymphoid Malignancies
OBJECTIVES:
- Determine the maximum tolerated dose and toxic effects of fludarabine when administered
with UCN-01 in patients with recurrent or refractory low-grade or indolent lymphoid
malignancies.
- Determine, preliminarily, the activity of this treatment regimen in these patients.
- Assess the pharmacokinetics of this treatment regimen in these patients.
OUTLINE: This is a dose-escalation study of fludarabine.
Patients receive UCN-01 IV over 72 hours on days 1-3 alone during course 1 and over 36 hours
on days 1-2 during courses 2-7. Patients also receive fludarabine IV over 30 minutes
beginning on day 1 and continuing for up to 5 days during courses 2-7. Courses repeat every
28 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of fludarabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.
Patients are followed every 2 months for 6 months, every 3 months for 1 year, and then every
6 months thereafter.
PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed recurrent or refractory low-grade or indolent lymphoid
malignancies requiring systemic therapy, including the following:
- Grade I or II follicular small cleaved cell lymphoma
- Small lymphocytic lymphoma/leukemia subtypes (chronic lymphocytic leukemia)
- Mantle cell lymphoma
- Waldenstrom's macroglobulinemia
- Lymphoplasmacytoid
- Marginal zone (nodal, extranodal, or splenic subtypes)
- Hairy cell leukemia
- Transformed indolent subtypes allowed provided 1 of the following criteria are met:
- Previously treated with a doxorubicin-containing regimen
- No rapidly progressing disease that threatens vital functions
- Measurable disease
- No active leptomeningeal or parenchymal CNS lymphoma NOTE: A new classification
scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of
"indolent" or "aggressive" lymphoma will replace the former terminology of "low",
"intermediate", or "high" grade lymphoma. However, this protocol uses the former
terminology.
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 50,000/mm^3
- No active Coomb's-positive hemolytic anemia
Hepatic:
- Total bilirubin less than 2.0 mg/dL (unless elevation is due to Gilbert's disease and
direct bilirubin is normal)
Renal:
- Creatinine less than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- No angina
- No congestive heart failure
- No myocardial infarction within the past 6 months
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No insulin-dependent diabetes mellitus
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- More than 3 weeks since prior systemic chemotherapy and recovered
Endocrine therapy:
- More than 3 weeks since prior systemic steroid therapy and recovered
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Wyndham H. Wilson, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
CDR0000067252
NCT ID:
NCT00019838
Start Date:
July 1999
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Waldenström macroglobulinemia
- refractory chronic lymphocytic leukemia
- refractory hairy cell leukemia
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent mantle cell lymphoma
- 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
- Leukemia
- Lymphoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
| NCI - Center for Cancer Research | Bethesda, Maryland 20892 |
