A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL

Prior treatment

• May not be receiving any other study agents
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. disease-free for at least 5 years and deemed to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated with curative intent within the past 5 years: cervical cancer in situ, localized prostate cancer, and basal cell or squamous cell carcinoma of the skin
• Foods or medications that are strong or moderate inhibitors or inducers of CYP3A taken within 1 week prior to study treatment and for the duration of the study

Other illness

• 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
• HIV-positive individuals, because of the potential for pharmacokinetic interactions with IPI-145
• Patients with a history of active tuberculosis within the preceding two years.
• Have had a Grade 2, 3 or 4 hemorrhage in the last 30 days
• History of alcohol abuse, chronic hepatitis, or other chronic liver disease (other than direct CLL liver involvement)

Lab values

• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN); direct bilirubin \>1.5 x ULN, unless due to hemolysis or Gilbert's syndrome
• Inadequate renal function defined by serum creatinine \>1.5 x ULN.
• Concurrent treatment with any agent known to prolong the QTc interval

Other

• Known CNS involvement
• Pregnant women are excluded from this study because IPI-145 has the potential for teratogenic or abortifacient effects.
• Baseline QTcF \>480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block
• Patients who have had a venous thromboembolic event (e.g., PE/DVT) requiring anticoagulation and who meet any of the following criteria:
• Have been on a stable dose of anticoagulation for \<1 month
• Are experiencing continued symptoms from their event
• Unable to receive prophylactic treatment for pneumocystis

• confirmed diagnosis of CLL and an indication for treatment as per IW-CLL 2008 criteria
• no prior therapy for CLL
• age 18-65 -- ECOG performance status ≤1