Protocol Number: 99-C-0127

Title:

Phase I and Pharmacokinetic Study of UCN-01 and Fludarabine in Relapsed or Refractory Low-Grade Lymphoid Malignancies

Number:

99-C-0127

Summary:

This study will test the safety and effectiveness of UCN-01, an experimental drug, together with fludarabine, a standard treatment for low-grade lymphomas and leukemias, in treating these cancers. Laboratory studies have shown that UCN-01 inhibits (slows or prevents) tumor cell growth and may also destroy some cells. Laboratory studies have also shown that when UCN-01 was combined with fludarabine, it increased fludarabine's effectiveness as much as 10 times.

Patients with low-grade relapsed lymphoma or leukemia who are candidates for this study will undergo various tests. These may include blood tests, X rays, CT and MRI scans, nuclear medicine scans, and bone marrow biopsy and aspiration to determine the extent of the patient's disease. For those accepted to the study, some or all of these tests will be repeated at various times during the study, for up to two years after treatment is completed.

Treatment will consist of up to six courses, or cycles, of UCN-01 and fludarabine given in combination. Each patient will first receive UCN-01 alone to determine if it is safe for that patient. Then, UCN-01 and fludarabine will be given together. UCN-01 will be infused through a vein over a period of 36 hours (except for the first course, which will take 72 hours) and fludarabine will be infused over 30 minutes. Fludarabine will be given from one to five days, starting the same day the UCN-01infusion begins. The cycle is repeated at four-week intervals.

Patients may also be asked to undergo additional bone marrow biopsy and aspirations and apheresis-a procedure to remove white blood cells-for research purposes, but these tests are not required to participate in the study.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Relapsed or refractory low-grade lymphoid malignancies (follicular small cleaved-grade I/II subtypes; marginal zone-nodal/extranodal/ splenic subtypes; small lymphocytic-lymphoma/leukemia subtypes (CLL); Waldenstrom's macroglobulinemia, mantle cell; lymphoplasmacytoid; Hairy cell leukemia.

Patients with transformed indolent subtypes are eligible providing they have previously received a doxorubicin-containing regimen or do not have rapidly progressive disease that threatens vital functions.

Histology confirmed by Laboratory of Pathology, NCI.

Requires systemic therapy.

Performance Status greater than or equal to 60%.

Age 18 years or older.

Creatinine less than 1.5 mg/dl or creatinine clearance greater than 60 ml/min; total bilirubin less than 2.0 mg/dl (patients with elevation of total bilirubin consistent with Gilbert's disease are eligible providing they have a normal direct bilirubin); ANC greater than or equal to 1000/mm(3); and platelet greater than or equal to 80,000/mm(3).

Measurable disease.

Recovered from acute effects of prior therapy.

Provides signed informed consent.

EXCLUSION CRITERIA:

HIV positive serology.

Pregnant or nursing. The effects of these agents on an unborn or breastfeeding child are unknown. Because there is a risk of detrimental effects on an unborn or breastfeeding child, pregnant or nursing women will be excluded fpr the study. Both male and female patients must be willing to use adequate contraception.

Active leptomeningeal or parenchymal CNS lymphoma.

Active Coombs + hemolytic anemia.

Systemic chemotherapy or systemic steroids within 3 weeks of study entry.

Diabetes mellitus requiring insulin treatment.

History of active coronary artery disease (defined by angina, congestive heart failure or myocardial infarction with 6 months).

Special Instructions: Currently Not Provided

Keywords:

Lymphoma

Drug Resistance

cDNA Microarray

Recruitment Keywords:

Lymphoid Malignancies

Lymphocytic Lymphoma

Walderstrom's Macroglobulinemia

Hairy Cell Leukemia

Conditions:

Chronic Lymphocytic Leukemia

Hairy Cell Leukemia

Leukemia

Lymphoma

Waldenstrom Macroglobulinemia

Investigational Drug(s):

UCN-01

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis

Multidrug resistance

Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy

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