Clinical trial NCT04217317: CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma
Official title: Pilot Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Relapsed T-Cell Lymphoma
Refractory T-Cell Lymphoma
Non Hodgkin Lymphoma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-01-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Number of Participants To Successfully Complete Therapy Regimen
timeFrame: up to 6 cycles, up to 24 weeks after first dose
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Patients are monitored for best overall response during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.
measure: Disease Control Rate
timeFrame: Patients are monitored for response during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.
measure: Duration of Response
timeFrame: Patients are monitored for response during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.
measure: Progression Free Survival
timeFrame: Patients are monitored for progression during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.
measure: Overall Survival
timeFrame: Maximum observed follow-up of 3 years 9 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Rakhee Vaidya, M.B.B.S.
role: PRINCIPAL_INVESTIGATOR
References: