Phase I Trial of STA-5312 Administered on Alternate Weekdays Every Two Weeks to Patients With Hematological Malignancies and Patients With Solid Tumors

Date de début de l'étude : 1 février 2004

Inclusion Criteria: * Male and female patients 18 years or older with one of the following malignancies: * Histologically or cytologically confirmed hematological malignancy (other than Acute Myeloid Leukemia and Myelodysplastic Syndrome) and if treatment is medically indicated, or, * Histologically-confirmed non-hematological malignancy that is metastatic or unresectable and for which no standard therapy is available. * Patients with CLL, PLL, CML, CTCL, ATL, and Non-Hodgkin's Lymphoma may be entered if they are refractory to or have relapsed following conventional chemotherapy regimens such as alkylating agents (e.g. chlorambucil and cyclophosphamide), anthracycline combinations \[e.g. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)\], and/or purine analogues (e.g. fludarabine monophosphate and 2-CDA) and are not currently being considered for re-treatment with conventional regimens * Patients with CLL and other leukemic malignancies will be staged according to the modified Rai staging criteria \[low-risk, intermediate-risk and high risk\]. All patients in the high-risk group (Stage III and IV) are eligible. Intermediate risk patients (Stage I and II) with one or more criteria of active disease (such as progressive lymphocytosis, lymphadenopathy, and splenomegaly, weight loss \> 10% within 6 months, extreme fatigue, fever and/or night sweats without evidence of infection, etc.) are also eligible * ECOG Performance Status of 0-2 * Life expectancy of greater than 12 weeks. * Patients must have acceptable organ and marrow function at screening and pre-dose visits as defined below unless approved medically by the clinical investigator. * Absolute neutrophils count greater than 1,000 cells/ul for patients with hematologic malignancies and ≥1,500 cells/ul for patients with solid tumors * Platelets greater than 100,000/ul * Hgb greater than 8.5 g/dL * Total bilirubin must be \<1.5 mg/dL or \< 2X upper limit of normal * AST (SGOT) \< 2.5 times the upper limit of normal * ALT (SGPT) \< 2.5 times the upper limit of normal * Adequate renal function (serum creatinine \< 2.0 mg/dL or a calculated creatinine clearance greater than 50 mL/min) * Electrocardiogram without evidence of clinically significant conduction abnormalities or active ischemia as determined by the investigator. * NCI grade 0-1 left ventricular ejection fraction within 30 days of dosing. * The effects of STA-5312 on the developing human fetus are unknown. Therefore, women of childbearing potential (defined as women under 50 years of age or history of amenorrhea for \< 12 months prior to study entry) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Women who are pregnant or lactating. * Patients who have had chemotherapy, radiotherapy (except palliative radiation delivered to \< 20% of bone marrow), immunotherapy, or corticosteroids ( \> 10 mg/day of prednisone or equivalent) within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * The use of nitrosoureas or mitomycin C within 6 weeks prior to study entry. * Patients with prior peripheral blood stem cell rescue or bone marrow transplantation. * History of primary brain tumors or active brain metastases. (Patients with previously treated brain metastases who are not receiving corticosteroids or anticonvulsants may be considered for enrollment) * History of stroke or other significant neurologic limitations within 6 months prior to study enrollment * Use of any investigational agents within 4 weeks of study enrollment. * History of severe allergic reactions to excipients (e.g. Tween 80) or had hypersensitivity reactions to other chemotherapeutic agents similar in structure to STA-5312. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator. * History of active CNS-lymphoma, AIDS-related lymphoma, or any uncontrolled severe medical illness or infection. * Grade 2 or higher sensory or motor neuropathy at screening. * Major surgery (excluding that for diagnosis) within 4 weeks of enrollment.