CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma

Inclusion Criteria:

• Patients must meet all of the following inclusion criteria before enrollment:

• Histologically or cytologically confirmed PTCL (all subtypes) or CTCL (mycosisfungoides/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, orintolerant to brentuximab vedotin.

• Patients with limited prior exposure to Bendamustine (less than 2 full cycles or ≤ 480 mg/m2) may be included, based on PI discretion.

• Patients must have measurable disease (e.g., a tumor mass >1 cm or evidence of bonemarrow 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 systemictherapy. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be asystemic therapy.

• Male and female patients 18 years of age and older

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Expected survival greater than 3 months.

• Women of child-bearing potential (i.e., women who are pre-menopausal or notsurgically sterile) must use accepted contraceptive methods (abstinence,intrauterine device [IUD], oral contraceptive or double barrier device) during thestudy, and must have a negative serum or urine pregnancy test within 1 week prior totreatment initiation.

• Fertile men must practice effective contraceptive methods during the study, unlessdocumentation of infertility exists.

• At least 2 weeks must have elapsed from prior chemotherapy drugs (other thansteroids) or radiation

• At least 6 weeks must have elapsed from prior autologous stem cell transplant and 12weeks must have elapsed from prior allogeneic stem cell transplant.

• Laboratory values ≤2 weeks must be: Adequate hematological function (absoluteneutrophil count [ANC] ≥1,500/mm3, platelets ≥100,000/mm3). In subjects with knownbone marrow involvement, ANC must be ≥ 1000/mm3 and platelets ≥75,000/mm3; Adequatehepatic function (aspartate aminotransferase [AST/SGOT] less than or equal to 3xupper normal limit [UNL], alanine aminotransferase [ALT/SGPT] less than or equal to 3x UNL (≤5x UNL if liver metastases present), bilirubin less than or equal to 1.5xUNL); Adequate renal function (serum creatinine less than or equal to 1.5 mg/dL or 133 µmol/L).

• No evidence of current infection.

• Mentally competent, ability to understand and willingness to sign the informedconsent form.

Exclusion Criteria:

• Patients with the following characteristics are excluded:

• 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 priorto initiation of treatment with study drugs (steroids are allowed)

• Patients with a history of allogeneic transplant must not have ≥ grade 3graft-versus-host disease (GVHD) or any clinically significant GVHD requiringsystemic immunosuppression.

• Serious medical illness that would potentially increase patients' risk for toxicity.

• Pregnant women, or women of child-bearing potential not using reliable means ofcontraception (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 heartfailure, symptomatic coronary artery disease, symptomatic angina pectoris,symptomatic myocardial infarction or symptomatic congestive heart failure.

• Evidence of current infection..

• Patients with known HIV infection, hepatitis B, or hepatitis C with positive viralload.

• Patients who have received cancer immunotherapy of any type within the past 2 weeksprior to initiation of CPI-613 treatment.