cpi-613 in combination with bendamustine in patients with relapsed/refractory t-cell non-hodgkin lymphoma

Conditions: Relapsed T-Cell Lymphoma; Refractory T-Cell Lymphoma; Non Hodgkin Lymphoma

Summary: the purpose of this study is to determine if it is possible to give cpi-613 with the drug bendamustine for 2 days every 28 days without causing severe side effects. in addition, this study will also test the safety of cpi-613 when given in combination with bendamustine.

primary objectives: a pilot study to evaluate the feasibility, safety and tolerability of a two day course per cycle of bendamustine plus cpi-613 in patients with relapsed and refractory t cell non-hodgkin lymphoma. exploratory objectives to evaluate: * overall response rate (orr) and disease control rate (dcr) derived from the lugano classification. * duration of response (dor) derived from the lugano classification. * progression-free-survival (pfs) derived from lugano classification. * overall survival (os). * single cell transcriptomics from pmbcs pre- and post-treatment; for correlative analyses of blood pbmc (and possibly excess pre-treatment tumor biopsy) cell population diversity and functional states to reveal potential mechanisms of drug treatment with regard to patient response status.

Eligibility criteria:
inclusion criteria: * patients must meet all of the following inclusion criteria before enrollment: * 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/m2) may be included, based on 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. * 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 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. * laboratory values ≤2 weeks must be: adequate hematological function (absolute neutrophil count \[anc\] ≥1,500/mm3, platelets ≥100,000/mm3). in subjects with known bone marrow involvement, anc must be ≥ 1000/mm3 and platelets ≥75,000/mm3; adequate hepatic function (aspartate aminotransferase \[ast/sgot\] less than or equal to 3x upper 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 1.5x unl); 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 informed consent 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 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 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.