Ibrutinib or Idelalisib in Treating Patients With Persistent or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma After Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To improve the outcomes of patients who have progressed or relapsed lymphoma or chronic
lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)/prolymphocytic leukemia (PLL)
within 180 days following allogeneic hematopoietic cell transplant (HCT) compared to
historical data: 12-month overall survival.

SECONDARY OBJECTIVES:

I. To describe the safety profile observed in these populations.

II. Estimate the overall response rate (complete response [CR] + partial response [PR]) by
standard morphologic, flow cytometric, imaging, and molecular techniques.

III. Assess progression free-survival.

IV. Define incidences of grade III-IV toxicities and infections.

V. Estimate incidence of relapse and non-relapse mortality.

VI. Estimate incidences of grade II-III and III-IV acute graft-versus-host disease (GVHD) and
chronic GVHD.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 or idelalisib PO twice
daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria:

- Patients with diagnoses of CLL/SLL or non-Hodgkin lymphoma (NHL) patients, who meet
the criteria of either relapse or progression at any time point after allogeneic HCT
or those who experience persistent stable disease or persistent disease with
regression between days 28 and 100 post-transplant using standard morphologic, flow
cytometric, and/or imaging studies and following the disease response evaluation
criteria established by the International Workshop on CLL (IWCLL) for CLL and those
following Cheson 2007 criteria for NHL

- Patients will then be assigned to one of two cohorts:

- Cohort 1 will include patients who have relapsed /progressed within the first 180
days post-transplant and who are still within 3 months from date of
progression-relapse

- Cohort 2 will include patients who have either i) relapsed/progressed beyond day
180 post-HCT, ii) those with persistent stable disease or persistent disease with
regression between days 28-100 after allogeneic HCT, or iii) those who progressed
or relapsed within 180 days after HCT but were not started on this protocol
within 3 months from date of progression or relapse could also be enrolled under
cohort 2

- NOTE: the inclusion of patients with persistent stable or persistent
regressing disease in this protocol is not meant to advocate treatment;
however, if the attending physician is inclined to offer treatment then
these patients would be eligible for this study

- Patients must be able to give informed consent

- Women of childbearing potential and men who are sexually active must affirm they are
practicing a highly effective method of birth control during and after the study
consistent with local regulations regarding the use of birth control methods for
subjects participating in clinical trials; men must agree to not donate sperm during
or after the study; for females, these restrictions apply for 1 month after the last
dose of study drug; for males, these restrictions apply for 3 months after the last
dose of the study drug

- Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [B-hCG]) or urine pregnancy test at screening

- Absolute neutrophil count (ANC) >= 750/mm^3

- Platelets >= 30,000/mm^3

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
of normal (ULN)

- Total bilirubin =< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of
non-hepatic origin

- Creatinine clearance (Clcr) > 25 mL/min

Exclusion Criteria:

- Pregnant or breast feeding females; (lactating females must agree not to breast feed
while taking ibrutinib or idelalisib)

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study should be first discussed and clarified
with the study investigators

- Concurrent use of other anti-cancer agents or treatments

- Known history of human immunodeficiency virus (HIV)

- Karnofsky performance status < 50%

- Active grades III or IV acute GVHD

- Central nervous system (CNS) involvement with disease refractory to intrathecal
chemotherapy

- Vaccinated with live, attenuated vaccines within 4 weeks of initiation of therapy

- Patients with other prior malignancies except for adequately treated basal cell
carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or
other cancer from which the patient has been disease-free for 5 years or greater,
unless approved by the protocol principal investigators

- Unable to swallow capsules or disease significantly affecting gastrointestinal
function and/or inhibiting small intestine absorption such as; malabsorption syndrome,
resection of the small bowel, or poorly controlled inflammatory bowel disease
affecting the small intestine

- Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment)

- Have uncontrolled hepatitis B or C infection

- IBRUTINIB-SPECIFIC EXCLUSION CRITERIA

- History of stroke or intracranial hemorrhage within 6 months of screening would be
exclusion for ibrutinib therapy but idelalisib would be an option

- Patients requiring anticoagulation with warfarin or equivalent vitamin K antagonists
(e.g., phenprocoumon) within 28 days from the start of study drug cannot be treated
with ibrutinib but idelalisib would be an option

- Patients requiring chronic treatment with strong cytochrome P450 family 3, subfamily A
(CYP3A) inhibitors cannot be treated with ibrutinib but idelalisib would be an option

- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by
the New York Heart Association Functional Classification would be exclusion for
ibrutinib therapy but idelalisib would be an option

- IDELALISIB-SPECIFIC EXCLUSION CRITERIA

- Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active
hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary
biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the
liver, or portal hypertension would be exclusion for idelalisib therapy but ibrutinib
would be an option

- Ongoing drug-induced pneumonitis would be exclusion for idelalisib therapy but
ibrutinib would be an option