CPI-613 and Bendamustine for the Treatment of Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma

Inclusion Criteria

• Histologically or cytologically confirmed PTCL (all subtypes) or CTCL (mycosis fungoides/Sezary syndrome) as defined by 2016 World Health Organization (WHO) classification
• For patients with PTCL: * Patients must have relapsed/ refractory disease to one or more systemic therapies * Patients with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin * Patients with limited prior exposure to bendamustine (less than 2 full cycles or =< 480 mg/m^2) may be included, based on principal investigator (PI) discretion * Patients must have measurable disease (e.g., a tumor mass > 1 cm or evidence of bone marrow involvement)
• For patients with CTCL, stage IB- IVB mycosis fungoides or Sezary syndrome are eligible * Patients must have relapsed/ refractory disease to at least one previous systemic therapy. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Expected survival > 3 months
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
• At least 2 weeks must have elapsed from prior chemotherapy drugs (other than steroids) or radiation
• At least 6 weeks must have elapsed from prior autologous stem cell transplant and 12 weeks must have elapsed from prior allogeneic stem cell transplant
• Absolute neutrophil count [ANC] >= 1,500/mm^3 (=< 2 weeks)
• Platelets >= 100,000/mm^3 (=< 2 weeks)
• In subjects with known bone marrow involvement, ANC must be >= 1000/mm^3 and platelets >= 75,000/mm^3 (=< 2 weeks)
• Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit [UNL] (=< 2 weeks) (=< 5 x UNL if liver metastases present)
• Alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 2 weeks) (=< 5 x UNL if liver metastases present)
• Bilirubin =< 1.5 x UNL (=< 2 weeks)
• Serum creatinine =< 1.5 mg/dL or 133 umol/L (=< 2 weeks)
• No evidence of current infection
• Mentally competent, ability to understand and willingness to sign the informed consent form

Exclusion Criteria

• Known cerebral metastases, central nervous system (CNS) or epidural tumor
• History of prior malignancy and considered to be at greater than 30% risk of relapse
• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of treatment with study drugs (steroids are allowed)
• Patients with a history of allogeneic transplant must not have >= grade 3 graft-versus-host disease (GVHD) or any clinically significant GVHD requiring systemic immunosuppression
• Serious medical illness that would potentially increase patients’ risk for toxicity
• Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown)
• Lactating females
• Fertile men unwilling to practice contraceptive methods during the study period
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
• Unwilling or unable to follow protocol requirements
• Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failure
• Evidence of current infection
• Patients with known human immunodeficiency syndrome (HIV) infection, hepatitis B, or hepatitis C with positive viral load
• Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment