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