Leukemia, Lymphoma
Conditions
Keywords
refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma
Brief summary
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
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.
Interventions
DRUGfludarabine phosphate
Sponsors
National Cancer Institute (NCI)
University Health Network, Toronto
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Countries
Canada
Outcome results
None listed