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

A Phase 1b/2 Study of IPI-145 in Combination With Fludarabine, Cyclophosphamide, and Rituximab (iFCR) in Previously Untreated, Younger Patients With Chronic Lymphocytic Leukemia.

This research study is evaluating a new drug called IPI-145 in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR), as a possible treatment for chronic lymphocytic leukemia (CLL).

Patients who fulfill eligibility criteria will be entered into the trial to receive IPI-145 in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR). After the screening procedures confirm participation in the research study:

Phase I

The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have CLL. Not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.

Phase II:

Patients treated with IPI-145 at the Recommended Phase II Dose (RP2D) + fludarabine, cyclophosphamide, rituximab (FCR) with standard dosing.

Inclusion Criteria:

• 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

Exclusion Criteria:

• May not be receiving any other study agents
• Known CNS involvement
• 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
• Pregnant women are excluded from this study because IPI-145 has the potential for teratogenic or abortifacient effects.
• 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
• HIV-positive individuals, because of the potential for pharmacokinetic interactions with IPI-145
• 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.
• Baseline QTcF >480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block
• Concurrent treatment with any agent known to prolong the QTc interval
• Patients with a history of active tuberculosis within the preceding two years.
• 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
• Have had a Grade 2, 3 or 4 hemorrhage in the last 30 days
• Are experiencing continued symptoms from their event
• History of alcohol abuse, chronic hepatitis, or other chronic liver disease (other than direct CLL liver involvement)
• 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
• Unable to receive prophylactic treatment for pneumocystis