Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma

PRIMARY OBJECTIVES:

I. Determine objective response rates of the SCR regimen (vorinostat, cladribine, and
rituximab) in B-cell malignancies.

II. Determine the tolerability and toxicities of the SCR regimen.

SECONDARY OBJECTIVES:

I. Evaluate progression free survival in patients treated with SCR. II. Estimate event free
survival for patients treated with SCR. III. Determine the contribution (if any) of
deoxyribonucleic acid (DNA) methylation/histone deacetylation to disease progression and/or
response to SCR combination chemotherapy.

IV. Perform scientific correlates to determine if SCR treatment a) is associated with global
and gene specific changes in transcription of messenger ribonucleic acid (mRNA)s and micro
ribonucleic acid (MiRNA)s b) is acting as an inhibitor of DNA methylation c) is activating or
silencing specific genes or miRNAs.

OUTLINE:

Patients receive vorinostat orally (PO) on days 1-14, cladribine intravenously (IV) over 2
hours on days 1-5, and rituximab IV on day 3 (weekly for the first course). Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up for 2 years and then every 6
months thereafter.

Inclusion Criteria:

- Patients must be able to provide informed consent according to institutional
guidelines

- Patients must have: 1) MCL; or 2) relapsed or refractory cluster of differentiation
(CD)20 positive B-cell indolent NHL; or 3) relapsed CLL

- Patients must have measurable disease/disease status requirements as follows:

- For CLL patients, symptomatic disease as defined by the International Workshop on
Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that mandate treatment

- For B-cell NHL patients must have at least one of the following to be eligible:

- Positron emission tomography (PET) avid or measurable disease by computed
tomography (CT) scan defined as at least 1 lesion that measures > 2 cm in a
single dimension

- Significant bone marrow and/or peripheral blood involvement by NHL (i.e. leukemic
phase) as determined by the investigator

- Patients with Waldenström macroglobulinemia (WM) are exempt from this requirement
if they have symptomatic hyperviscosity or clinically relevant cytopenias and
elevated serum immunoglobulin M (IgM)

- Patients must have adequate bone marrow reserve as indicated by an absolute neutrophil
count (ANC) > 1.500/mm^3 and platelet count > 150.000/mm^3 if no bone marrow
involvement; however, if there is significant lymphoma/leukemia bone marrow
infiltration, no pre-existing hematologic parameters must be met

- Patients must have a performance status of 0, 1, or 2 according to Eastern Cooperative
Oncology Group

- Serum creatinine < 2.0 mg/dL or estimated glomerular filtration rate (GFR) > 60 mL/min

- Serum bilirubin =< 1.5 × upper limit of normal (ULN)

- Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × ULN

- Alkaline phosphatase =< 2.5 × ULN

- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment

- Male and female patients must agree to use an effective contraceptive method during
the study and for a minimum of 6 months after study treatment

Exclusion Criteria:

- Significant hypersensitivity to cladribine or vorinostat; hypersensitivity to
rituximab infusion is not an exclusion criterion; however, appropriate changes to
infusion schedules will be made based on current or prior reactions

- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol

- Patients with a diagnosis of a relapsed/refractory aggressive cluster of
differentiation antigen 20 (CD20)+ B-cell neoplasm defined as Burkitt's lymphoma or
diffuse large B-cell lymphoma

- A diagnosis of acute lymphoplasmic leukemia, and lymphoblastic lymphoma

- Use of investigational agents or any anticancer therapy within 2 weeks before study
entry with the exception of hydroxyurea and steroids; the patient must have recovered
from all acute toxicities from any previous therapy

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver, or other organ system that
may place the patient at undue risk to undergo treatment

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment)

- Pregnant or lactating patients

- Any significant concurrent disease, illness, or psychiatric disorder that would
compromise patient safety or compliance, interfere with consent, study participation,
follow up, or interpretation of study results

- Patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency
virus (HIV) associated complex are not eligible for treatment

- Patients with active hepatitis B or C are not eligible for the study

- Patients taking other histone deacetylases (HDAC) inhibitors; for example, patients
taking valproic acid, there must be a 14 day washout period prior to enrollment in
this study