Carfilzomib and Umbralisib in Treating Patients with Relapsed or Refractory Lymphoma

Inclusion Criteria

• PHASE I: Patients with relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma; patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are also eligible; in addition, patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies; patients with DLBCL and Hodgkin lymphoma (HL) will be eligible if there is no available standard therapy
• PHASE Ib: Patients must have histologically confirmed R/R PTCL or C-MYC positive DLBCL (as defined by World Health Organization [WHO] criteria and immunohistochemistry [IHC] staining of C-MYC); the patients with PTCL or DLBCL will be eligible if there is no available standard therapy.
• Must have received front-line chemotherapy; no upper limit for the number of prior therapies; patients may have relapsed after prior autologous stem cell transplant or allogeneic stem cell transplant
• Evaluable disease in the phase I, and measurable disease for the phase Ib study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,000/dL
• Platelets >= 75,000
• Total bilirubin =< 1.5 X institutional limits; subjects with Gilbert's syndrome may have a bilirubin > 1.5 x upper limit of normal (ULN); activated partial thromboplastin time (aPTT), prothrombin time (PT) not to exceed 1.2 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.0 X institutional upper limit of normal
• Serum creatinine within normal institutional limits
• Measured creatinine clearance >= 50 mL/min/for patients with creatinine levels above institutional normal.
• Left ventricular ejection fraction (LVEF) > 50% as defined by echocardiography (ECHO) or multigated acquisition scan (MUGA).
• Negative urine or serum pregnancy test for females of childbearing potential; all females of childbearing potential must use an effective barrier method of contraception (either an intrauterine device [IUD] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter; male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior Therapy * Exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier * Systemic steroids that have not been stabilized (>= 5 days) to the equivalent of =< 10 mg/day prednisone prior to the start of the study drugs * No other concurrent investigational agents are allowed
• Central nervous system metastases, including lymphomatous meningitis will be allowed in the phase II study, but will not be allowed in the phase I
• History of allergic reactions to TGR-1202 or carfilzomib
• Uncontrolled intercurrent 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
• Pregnant women
• Nursing women
• Active concurrent malignancy (except non-melanoma skin cancer, carcinoma in situ of the cervix, low risk prostate cancer); if there is a history of prior malignancy, the patient must be disease-free for >= 2 years
• Patients with a low grade lymphoma or CLL and a concurrent high grade lymphoma transformed from the low grade lymphoma or CLL will be eligible
• Patients known to be human immunodeficiency virus (HIV)-positive
• Patients with active hepatitis A, hepatitis B, or hepatitis C infection
• Concomitant use of CYP3A4 inhibitors
• Significant cardiac abnormalities such as: * Myocardial infarction within 6 months of course 1 day 1 (C1D1) * An electrocardiogram (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not coronary artery disease (CAD) is present; * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 50% defined by multigated acquisition scan (MUGA) and echocardiogram (ECHO)
• A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter-defibrillator (AICD)