Clinical Trials /

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

NCT04217317

Description:

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.

Related Conditions:
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IRB00062873
  • SECONDARY ID: WFBCCC 28419
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT04217317

Conditions

  • Relapsed T-Cell Lymphoma
  • Refractory T-Cell Lymphoma
  • Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CPI 613devimistatCPI-613 in Combination with Bendamustine
BendamustineBendeka, Treanda, Bendamustine HydrochlorideCPI-613 in Combination with Bendamustine

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
CPI-613 in Combination with BendamustineExperimentalCPI-613 at 2500 mg/m2 is infused intravenously (IV) via a central catheter over 2 hrs on Days 1and 2. Bendamustine at 90 mg/m2 is infused IV over 10 minutes on Days 1 and 2 of each treatment cycle, given immediately after CPI-613 administration.
  • CPI 613
  • Bendamustine

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants To Successfully Complete Therapy Regimen
Time Frame:8 weeks after first dose
Safety Issue:
Description:Feasibility will be defined as 75% of patients being successfully able to complete 80% of their therapy regimens. Toxicity data will be collected on all patients who receive at least one dose of treatment on the study

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:Up to 12 weeks post treatment
Safety Issue:
Description:Overall response rate is defined as the proportion of patients who achieve a best overall response complete response or partial response during or following study treatment according to the Lugano Classification (Stage I - involvement in a single lymph node region to Stage IV diffuse or disseminated involvement of one or more extranodal organs or tissue).
Measure:Disease Control Rate
Time Frame:Up to 12 weeks post treatment
Safety Issue:
Description:Disease control rate defined as the proportion of patients who achieve a best overall response of complete response, partial response, or stable disease (SD). Best overall response of stable disease must have met the response stable disease criteria at least once ≥12 weeks after start of study treatment.
Measure:Duration of Response
Time Frame:Up to 12 weeks post treatment
Safety Issue:
Description:Duration of Response will be defined for responders (patients with a best overall response of complete response or partial response). It is the time from the date of the first documented complete response or partial response until the date of the first date of progressive disease, or death due to any cause, whichever occurs first. If a patient has not progressed or died by the analysis cutoff date, duration of response will be censored at the time of the last adequate tumor assessment on or before the cutoff date.
Measure:Progression Free Survival
Time Frame:Up to 12 weeks post treatment
Safety Issue:
Description:Progression free survival defined as the time from the start of study treatment until the first date of progressive disease, or death due to any cause, whichever occurs first. If a patient has not progressed or died by the analysis cutoff date, progression free survival will be censored at the time of the last adequate tumor assessment on or before the cutoff date.
Measure:Overall Survival
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Overall survival is measured from the start of study treatment until death due to any cause. If a patient is not known to have died at the date of the analysis cut-off, overall survival will be censored at the last date that: Patient is documented to be alive. At the time of single cell sequencing.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

June 8, 2020