NCT04217317TerminatedPhase 2
Pilot Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma
Wake Forest University Health Sciences1 site in 1 country6 target enrollmentStarted: September 16, 2020Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Number of Participants To Successfully Complete Therapy Regimen
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
Arms & Interventions
CPI-613 in Combination with Bendamustine
Experimental
CPI-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.
Intervention: CPI 613 (Drug)
CPI-613 in Combination with Bendamustine
Experimental
CPI-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.
Intervention: Bendamustine (Drug)
Outcomes
Primary Outcomes
Number of Participants To Successfully Complete Therapy Regimen
Time Frame: up to 6 cycles, up to 24 weeks after first dose
Number of patients successfully able to complete 80% (at least 5 of 6 planned cycles) of their therapy regimens.
Secondary Outcomes
- Overall Response Rate(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.)
- Disease Control Rate(Patients are monitored for response during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.)
- Duration of Response(Patients are monitored for response during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.)
- Progression Free Survival(Patients are monitored for progression during and after study treatment. Follow-up for response ranged from 2 to 6 months after start of treatment.)
- Overall Survival(Maximum observed follow-up of 3 years 9 months)
Investigators
Study Sites (1)
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