UCN-01 and Fludarabine in Treating Patients With Recurrent or Refractory Lymphoma or Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given with UCN-01 in treating patients with recurrent or refractory low-grade lymphoma or leukemia.

Detailed Description
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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.

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

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: 7-hydroxystaurosporine
* Drug: fludarabine phosphate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 7-hydroxystaurosporine|nan|
|Drug: fludarabine phosphate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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