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

Pilot Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma

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.

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.