This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with relapsed lymphoma. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Determine the objective response rate (ORR) of MK-2206 (Akt inhibitor MK2206) in patients with relapsed/refractory lymphoma.

SECONDARY OBJECTIVES:

I. Assess the progression free survival (PFS) of MK-2206 in patients with relapsed/refractory lymphoma.

II. Assess the safety and tolerability of MK-2206 monotherapy. III. Examine pretreatment phosphorylated v-akt murine thymoma viral oncogene homolog 1 (pAkt) protein expression by immunohistochemistry, and correlate the results with treatment response.

IV. Examine the effect of therapy on serum cytokines and chemokines that regulate the tumor-promoting inflammatory process and/or immunity in patients with relapsed/refractory lymphoma, and correlate the results with treatment response.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

• Histologically confirmed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma may be included)
• Relapsed or refractory after at least one regimen and with no curative option with conventional therapy
• Bidimensionally measurable disease (at least 2 cm)
• No evidence of cerebral or meningeal involvement by lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Signed informed consent form prior to enrollment
• Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a women become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately

Exclusion Criteria:

• Burkitt's lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia and cutaneous T-cell lymphoma
• Chemotherapy or radiation therapy or other investigational agents within 3 weeks prior to entering the study unless there is clear evidence of progression of disease and toxicity from previous treatment has resolved in which case study entry may be within 1 week of last treatment
• Previous radioimmunotherapy within 12 weeks
• Patients with known immunodeficiency virus (HIV) infection must not have cluster of differentiation (CD)4 cells < 400/mm^3 and who must not have a prior acquired immunodeficiency syndrome (AIDS)-defining diagnosis and cannot be on antiretroviral therapy for HIV
• Known active viral hepatitis
• Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or with compliance with the study
• Absolute neutrophil count < 1.5 x 10^9/L
• Platelets < 75 x 10^9/L
• Total bilirubin > 1.5 x upper limit of normal (ULN) (> 3 x ULN for patients with liver involvement)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.5 x ULN (> 5 x ULN for patients with liver involvement)
• Serum creatinine > 2 x ULN
• Hemoglobin (Hb)A1C > 8%
• Patients receiving any medications or substances that are inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP 450 3A4) are ineligible
• Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
• Cardiovascular: baseline Fredericia corrected QT interval (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
• Significant heart block or baseline bradycardia < 50 beats per minute (bpm) due to cardiac disease
• Patients who are pregnant or breastfeeding