Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining UCN-01 with fludarabine in treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic lymphoma.

Detailed Description
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OBJECTIVES: Determine the overall response rate in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and fludarabine. Assess the molecular changes in CLL cells in peripheral blood in patients treated with this regimen. Determine the progression-free and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter, dose-escalation study of UCN-01. Patients receive UCN-01 IV over 3 hours on day 1 and fludarabine IV over 30-60 minutes on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 18-46 additional patients receive UCN-01 and fludarabine as above at the recommended phase II dose. PROJECTED ACCRUAL: A total of 12 patients will be accrued for the phase I portion of this study within 6 months. A total of 18-46 patients will be accrued for the phase II portion of this study within 9-23 months.

Official Title
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Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma

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 or cytologically confirmed chronic lymphocytic leukemia (CLL) or B-cell small lymphocytic lymphoma (SLL) CLL is defined as: Persistent lymphocytosis greater than 5,000/mm^3 CD19/CD5/CD23 positive Kappa or lambda light chain restriction Refractory to or disease progression after 1 or 2 prior treatment regimens Retreatment with oral chlorambucil is allowed and considered a second regimen At least one of the chlorambucil treatments must be for 3 months or longer At least 4 courses of cyclophosphamide, vincristine, and prednisone with or without doxorubicin allowed Patients may have received prior fludarabine as first- or second-line therapy if there is evidence of at least partial response and time to progression after initial fludarabine therapy was at least 12 months No CNS involvement by lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy More than 3 months Hematopoietic See Disease Characteristics Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 No autoimmune hemolytic anemia or thrombocytopenia secondary to CLL or SLL requiring ongoing therapy with prednisone or other immunosuppressive agents Hepatic Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Pulmonary DLCO greater than 60% predicted FEV_1 greater than 70% predicted No significant underlying pulmonary disease Other No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No insulin-dependent diabetes mellitus No other uncontrolled concurrent illness No ongoing or active infection No pre-existing peripheral neuropathy grade 2 or greater No psychiatric illness or social situation that would preclude study compliance No prior allergic reactions to compounds of similar chemical or biological composition to UCN-01 or other agents in this study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy and recovered Endocrine therapy See Hematopoietic Radiotherapy No prior mediastinal radiation At least 4 weeks since prior radiotherapy and recovered Surgery Not specified Other No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients

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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refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma