INCLUSION CRITERIA:
Patients with histologically documented (by the NIH pathology department) solid tumors and lymphoid malignancies (lymphoma and CLL) who are refractory to standard therapy or who have no acceptable standard treatment options. Patients with lymphoid malignancies will be eligible if their disease has progressed following 2 standard therapies (aggressive NHL), and if their disease is considered refractory (for indolent NHL).
Patients must have measurable or evaluable disease.
Patients must have recovered to at least Grade less than or equal to1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, or UCN-01). Patients must be greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase Zero study. Patients must be greater than or equal to 1 month since any prior radiation or major surgery. However, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy.
Age greater than or equal to 18 years
The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
Life expectancy greater than 3 months
Patients must have normal or adequate organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1,500/milliliter
- Platelets greater than or equal to 100,000/milliliter
- Total bilirubin* within less than or equal to 1.5 times upper limit of normal
- AST (SGOT)/ALT (SGPT) less tan or equal to 2.5 times institutional upper limit of normal
- creatinine less than 1.5 times upper limit of normal
OR
- creatinine clearance greater than or equal to 60 mL/min (measured) for patients with creatinine levels greater than or equal to 1.5 times upper limit of normal.
*we will allow patients with Gilbert's syndrome with total bilirubin up to 2.5 mg/dL
The effects of SNX-5422 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 2 months after discontinuation from the study. Women of childbearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SNX-5422, breastfeeding should be discontinued if the mother is treated with SNX-5422.
Ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Patients receiving any other investigational agents. Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (AHA Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible PK interactions with SNX-5422. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that SNX-5422 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to SNX-5422.
Chronic diarrhea.
Gastrointestinal diseases that could affect drug absorption, including postsurgical states such as gastric bypass.
Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009