Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

PRIMARY OBJECTIVES:

I. To explore the cellular and molecular mechanisms of idelalisib-induced diarrhea/colitis in
relapsed chronic lymphocytic leukemia (CLL), relapsed indolent non-hodgkin lymphomas (iNHL),
or relapsed small lymphocytic lymphoma (SLL).

II. To further understand the mechanism of action (MOA) of idelalisib in context of the nodal
microenvironment and the possible involvement of the immune system in idelalisib's
anti-lymphoma activity.

OUTLINE:

Patients receive a physical examination during visit 1. A stool sample, blood sample, and 6
biopsies are collected at visit 2, and patients undergo a flexible fiberoptic sigmoidoscopy.
Patients receive idelalisib orally (PO) twice daily (BID) after visit 2. Treatment continues
in the absence of disease progression or unacceptable toxicity. A third research visit occurs
upon development of idelalisib-associated diarrhea/colitis symptoms. Patients with
diarrhea/colitis symptoms undergo a full colonoscopy and collection of stool and blood
samples. Control patients with no diarrhea/colitis symptoms undergo all needed tests and
assessments including a flexible fiberoptic sigmoidoscopy and collection of stool and blood
samples. All patients undergo optional biospecimen collection at the time of disease
progression.

Inclusion Criteria:

- Food and Drug Administration (FDA)-approved indications for idelalisib of relapsed,
histologically confirmed B-cell indolent non-hodgkin lymphoma (iNHL) or chronic
lymphocytic leukemia (CLL)

- For iNHL: measureable nodal disease, defined as the presence of >= 1 nodal lesion that
measures >= 2 cm in a single dimension as assessed by computed tomography (CT) or
magnetic resonance imaging (MRI)

- Discontinuation of all other therapies (including radiotherapy or chemotherapy) for
the treatment of iNHL >= 3 weeks before initiation of study treatment

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Absolute neutrophil count > 750

- Platelets > 50,000

- Total bilirubin < 2 X institutional upper limit of normal (ULN)

- Aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine
transferase (ALT) serum glutamate pyruvate transaminase (SPGT) < 3 X institutional ULN

- Creatinine < 2 X institutional ULN

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days following completion of therapy;
should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent; all
patients must have signed, witnessed informed consent prior to registration

Exclusion Criteria:

- Prior exposure to idelalisib

- Known histological transformation from iNHL to diffuse large B-cell lymphoma or
Richter's Transformation for CLL

- Ongoing treatment with any other investigational agents

- Known central nervous system (CNS) involvement of lymphoma (CNS staging not required)

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to idelalisib

- Uncontrolled inter-current illnesses 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

- Known human immunodeficiency virus (HIV) infection (HIV testing not required)

- Known John Cunningham (JC) virus infection and/or progressive multifocal
leukoencephalopathy (PML)

- Clinically active hepatitis A, B, or C infections

- NOTE: Patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV)
infection may enroll if other laboratory criteria are met; those with HBV surface
antigen positivity may enroll only if maintained on appropriate suppressive antiviral
therapy for the duration of enrollment in the trial

- Pregnancy or active nursing of an infant