Safety and Activity of SNX-5422 Plus Ibrutinib in CLL

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
• A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.
• No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
• Presence of mutated BTK in ≥ 4% of peripheral blood or bone marrow CLL cells, or ≥1% and rising on two separate measurements obtained at least 28 days apart.
• Life expectancy of at least 9 months
• Karnofsky performance score 70
• Adequate baseline laboratory assessments
• Signed informed consent form
• Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia
• Subjects with reproductive capability must agree to practice adequate contraception methods.

Exclusion Criteria:

• Subjects experiencing toxicity with ibrutinib
• Prior treatment with any Hsp90 inhibitor.
• Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
• Conventional chemotherapy or radiation within 4 weeks.
• The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
• Screening ECG QTc interval 470 msec for females, 450 msec for males.
• At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
• Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
• Gastrointestinal diseases or conditions that could affect drug absorption
• Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• History of documented adrenal dysfunction not due to malignancy.
• History of chronic liver disease.
• Active hepatitis A or B.
• Current alcohol dependence or drug abuse.
• Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
• Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
• Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.