Enzalutamide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

This pilot clinical trial studies enzalutamide in treating patients with mantle cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Androgens can cause the growth of cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgen made by the body.

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.

Eligibility Criteria:
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