Enzalutamide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Condition: Ann Arbor Stage I Mantle Cell Lymphoma; Ann Arbor Stage II Mantle Cell Lymphoma; Ann Arbor Stage III Mantle Cell Lymphoma; Ann Arbor Stage IV Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Enzalutamide; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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