Clinical Trials /

A Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL)

NCT04171791

Description:

The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.

Related Conditions:
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL)
  • Official Title: A Single Arm, Open-Label Pilot Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL) Stage IB to IV

Clinical Trial IDs

  • ORG STUDY ID: 2000022803
  • NCT ID: NCT04171791

Conditions

  • CTCL

Interventions

DrugSynonymsArms
ABT-199 (venetoclax)ABT-199 (Venetoclax)

Purpose

The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.

Detailed Description

      This is a single arm, open-label, non-randomized study with venetoclax (ABT-199) in CTCL
      patients (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed
      mycosis fungoides). This study is planned to be conducted in 18 patients, 18 years or older
      in age, undergoing a 5-week dose escalation protocol (per the US FDA package insert
      guidelines of venetoclax for CLL). Safety monitoring will continue throughout the whole
      period of drug administration and the treatment will be discontinued if intolerable toxicity
      (defined in Stopping Rules) or disease progression occurs during this period.
    

Trial Arms

NameTypeDescriptionInterventions
ABT-199 (Venetoclax)ExperimentalPatients with Cutaneous T Cell Lymphoma (CTCL) will receive ABT-199 (Venetoclax).
  • ABT-199 (venetoclax)

Eligibility Criteria

        Inclusion Criteria:

          -  Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary syndrome only, and
             excluding transformed mycosis fungoides), stage IB-IV (hereafter referred to as
             advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable.

          -  All subjects must have shown disease refractory to one or more standard systemic
             therapy (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or
             total skin electron beam therapy over 3 months, or have demonstrated relapsed or
             progressive disease at any time while receiving one or more of therapies.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          -  Adequate bone marrow function: WBC > 2000/µL; platelet count > 75,000/mm3; Neutrophil
             count > 1000/µL, without use of colony stimulating factors (CSF).

          -  Required washout period for prior therapies

               1. Spot Skin Radiation Therapy (≤10% skin surface): 4 weeks

               2. Systemic therapy: 4 weeks, or until recovered from toxicities

          -  Women of child-bearing potential must have negative serum pregnancy test and use
             accepted highly effective methods of birth control throughout the study and for 90
             days after dosing and must agree to use effective contraception, such as hormonal
             birth control (must be at least 3 years without complications), intrauterine devices,
             double barrier method (condom plus spermicide or diaphragm), or abstain from sexual
             intercourse.

          -  Male patients must be willing to use an appropriate method of contraception (e.g.,
             condoms) or abstain from sexual intercourse and inform any sexual partners that they
             must also use a reliable method of contraception during the study and for 90 days
             after dosing.

          -  Adequate hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), AST ≤3.0 x
             ULN, ALT ≤ 3.0 x ULN

          -  Adequate renal function: creatinine clearance ≥ 50 mL/min

          -  Ability to comply with the treatment schedule

        Exclusion Criteria:

          -  Extracutaneous disease except blood, bone marrow and lymph nodes.

          -  Concomitant use of any systemic anti-cancer therapy or immune modifier.

          -  Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of
             initiation of study drug administration.

          -  Patients receiving P-gp inhibitors are not eligible for inclusion unless these agents
             are discontinued for a washout period of 4 weeks. Patients who are taking medications
             that are narrow window index P-gp substrates (e.g. digoxin, fexofenadine, loperamide,
             quinidine, talinolol, vinblastine) are not eligible for enrollment.

          -  Patients with biopsy confirmed transformed MF.

          -  Prior allogeneic hematopoietic cell transplant.

          -  Any ongoing infection requiring antibiotics within 2 weeks prior to the start of the
             study drug, except for antibiotics (e.g. cephalexin) prescribed superficial skin
             infection.

          -  Known history of human immunodeficiency virus (HIV), hepatitis B or C.

          -  History of prior malignancy with the exception of cervical intraepithelial neoplasia,
             non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA
             <1.0). Patients with a history of other malignancies must have undergone potentially
             curative therapy and have no evidence of that disease for five years.

          -  Uncontrolled intercurrent illness, condition, or circumstances that could limit
             compliance with the study including, but not limited to, the following: acute or
             chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or
             psychiatric conditions.

          -  Major surgery within 8 weeks of enrollment.

          -  Medically significant cardiac event or unstable cardiovascular function defined as:

          -  Symptomatic ischemia, unstable angina pectoris

          -  Uncontrolled clinically significant cardiac arrhythmia

          -  Symptomatic heart failure NYHA Class ≥ 3

          -  Myocardial infarction or cardiac surgery within 6 months prior to enrollment

          -  Cerebrovascular event (transient ischemic attack, stroke or CNS bleeding) within the
             last 12 months.

          -  Major bleeding within the last 6 months.

          -  Use of any investigational agents within 30 days prior to enrollment and for the
             duration of the study.

          -  Pregnant or lactating.

          -  Unwilling or unable to provide informed consent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Body Temperature
Time Frame:Up to 32 weeks
Safety Issue:
Description:Safety and tolerability endpoints will be evaluated on the basis of body temperature.

Secondary Outcome Measures

Measure:Skin Clinical Response
Time Frame:Up to 32 weeks
Safety Issue:
Description:Exploratory skin clinical responses measured by a modified severity-weighted assessment tool (mSWAT).
Measure:Duration of Response
Time Frame:Up to 32 weeks
Safety Issue:
Description:Duration of response to treatment will be measured in weeks.
Measure:Relapse Free and Progression Free Survival
Time Frame:Up to 32 weeks
Safety Issue:
Description:Relapse free and progression free survival based on every 4 week follow up after the initial dose until one of the events occurs first: Progressive disease (PD) is documented, another anticancer treatment is administered and/or 28 weeks are completed after the patient's first dose of venetoclax.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yale University

Last Updated

January 14, 2021