Enzalutamide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVES:

I. Perform a preliminary assessment of the efficacy of single-agent enzalutamide, based on
overall response rate, in subjects with relapsed/refractory mantle cell lymphoma (MCL) or
previously untreated MCL.

SECONDARY OBJECTIVES:

I. To evaluate the duration of disease control (progression free survival) in patients with
MCL treated with enzalutamide.

II. To evaluate the safety profile of enzalutamide in MCL.

III. To gain preliminary data on clinical activity and toxicity of this regimen in male
versus (vs.) female patients.

OUTLINE:

Patients receive enzalutamide orally (PO) once daily (QD). Courses 1-3 repeat every 4 weeks
(28 days) and subsequent courses repeat every 12 weeks (84 days) in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Inclusion Criteria:

- Patients must have histologically confirmed relapsed/refractory or previously
untreated mantle cell lymphoma (any stage)

- Patients with untreated MCL should be asymptomatic or minimally symptomatic from their
MCL and without aggressive clinicopathological features that would otherwise warrant
immediate intensive therapy; these will generally be patients who qualify for an
initial period of "watch and wait" per clinical discretion

- Patients must have metabolically active (positron emission tomography [PET] scan
positive) measurable disease (defined as lesions greater than 1.5 cm long axis that
can be accurately measured in two dimensions by computed tomography [CT])

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-2

- Absolute neutrophil count (ANC) >= 1000/mm^3 or >= 750/mm^3 in the setting of marrow
involvement by disease (independent of growth factor or transfusion support)

- Platelets >= 50,000/mm^3 or >= 30,000/mm^3 in the setting of marrow involvement by
disease or splenomegaly due to disease (independent of growth factor or transfusion
support)

- 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 (CrCl) >= 30 mL/min (as calculated by Cockcroft-Gault equation)

- All patients must be informed of the investigational nature of this study and have
given written consent in accordance with institutional and federal guidelines; patient
must sign an informed consent document indicating that they understand the purpose of
and procedures required for the study, and are willing to participate in and comply
with the guidelines of the study

- Women of childbearing potential and men who are sexually active must affirm they are
practicing a highly effective method of barrier 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; these restrictions apply throughout the treatment period and for
three months after the last dose of enzalutamide

- Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant
or breastfeeding are ineligible for this study

Exclusion Criteria:

- Uncontrolled 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 within 6 months of enrollment

- Known active central nervous system lymphoma

- Known clinically significant heart disease as evidenced by:

- Myocardial infarction within 6 months of enrollment

- Uncontrolled angina within 6 months of enrollment

- Congestive heart failure New York Heart Association (NYHA) class III or IV, or a
history of congestive heart failure NYHA class III or IV in the past, unless a
screening echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 3
months results in a left ventricular ejection fraction >= 45%

- Clinically significant ventricular arrhythmias

- History of Mobitz II second degree or third degree heart block without a
permanent pacemaker in place

- Bradycardia as indicated by a heart rate < 50 beats per minute at screening visit

- Hypotension as indicated by systolic blood pressure (SBP) =< 85 on 2 consecutive
measurements at screening visit

- Uncontrolled hypertension as indicated by SBP > 170 mmHg or diastolic blood
pressure (DBP) > 105 mmHg on 2 consecutive measurements at screening visit

- Child Pugh class C hepatic dysfunction

- History of seizures

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of enzalutamide, or put the study outcomes at undue risk

- 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 investigator / lead-sub-investigator

- Chemotherapy, immunotherapy, biologically targeted therapy, other investigational
agent, or radiation therapy within 3 weeks of initiation of enzalutamide therapy; for
patients with objectively progressive disease on a Bruton tyrosine kinase
(BTK)-targeting agent whom in the opinion of the investigator would not tolerate a 21
day washout period, a > 5 half-lives washout period will be allowed

- Prior allogeneic transplant with graft-versus-host disease (GVHD) requiring ongoing
immunosuppressive therapy

- Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral
therapy are ineligible

- Ongoing treatment with hormonal agents (e.g. finasteride, dutasteride, ketoconazole,
hormonal birth control, estrogen replacement therapy, testosterone replacement
therapy) or herbal products that may have hormonal activity (saw palmetto, black
cohosh); patients taking these agents are eligible for screening, but must be willing
to undergo a washout period of 4 weeks prior to starting study treatment