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.
