Clinical Trials /

Venetoclax in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma

NCT03534180

Description:

This phase II trial studies the side effects and best dose of venetoclax and to see how well it works in treating patients with mature T-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Venetoclax in Treating Participants With Recurrent or Refractory Mature T-Cell Lymphoma
  • Official Title: A Phase 2 Study of Venetoclax With Safety Lead-In for Treatment of Relapsed/Refractory Mature T-Cell Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 18119
  • SECONDARY ID: NCI-2018-00810
  • SECONDARY ID: 18119
  • NCT ID: NCT03534180

Conditions

  • Recurrent Mature T- Cell and NK-Cell Non-Hodgkin Lymphoma
  • Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
VenetoclaxABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, VenclyxtoTreatment (venetoclax)

Purpose

This phase II trial studies the side effects and best dose of venetoclax and to see how well it works in treating participants with mature T-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety and tolerability of venetoclax, including the dose ramp-up, in adults
      with relapsed or refractory mature T-cell lymphoma. (Safety Lead-in) II. To estimate the
      overall response rate (ORR) of venetoclax in patients with relapsed or refractory mature
      T-cell lymphoma. (Phase 2)

      SECONDARY OBJECTIVES:

      I. To evaluate the complete response rate, duration of response, time to response, overall
      survival and progression free survival of venetoclax in relapsed/refractory mature T-cell
      lymphoma. (Phase 2) II. To further characterize the safety and toxicities of venetoclax in
      relapsed/refractory mature T-cell lymphoma. (Phase 2)

      EXPLORATORY OBJECTIVE:

      I. To determine changes in Bcl-2 gene expression in pre- and post-treatment tumor samples of
      mature T- cell lymphoma.

      OUTLINE: This is a safety lead-in dose-escalation study, followed by a phase II study.

      Participants receive venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats
      every 28 days for up to 26 cycles in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, participants are followed up periodically for up to 24
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (venetoclax)ExperimentalParticipants receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Documented informed consent of the participant and/or the legally authorized
             representative

          -  Be willing to provide tissue

          -  Eastern Cooperative Oncology Group (ECOG) =< 2

          -  Resolution of all acute toxic effects of prior therapy or surgical procedures to
             Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 (except alopecia)

          -  Failed at least 2 prior systemic therapies

          -  Histologically confirmed peripheral T-cell lymphoma (PTCL) as defined by the World
             Health Organization (WHO) criteria 2016, excluding cutaneous T-cell lymphoma (CTCL);
             transformed mycosis fungoides is allowed

          -  Measurable disease defined as:

               -  Computed tomography (CT)/magnetic resonance imaging (MRI)/ or positron emission
                  tomography (PET) scan, with at least one nodal site of disease which is 1.5 cm in
                  longest dimension, and/or spleen > 13 cm in vertical length, and/or diffuse
                  enlargement of liver with or without focal nodules (Lugano 2014); extra nodal
                  sites with biopsy proven abnormal lesions are allowed including skin

               -  Patients with only bone marrow involvement will be acceptable

          -  Prior stem cell transplant allowed

               -  If allogeneic hematopoietic cell transplantation (HCT) must have recovered from
                  acute toxicity

               -  Cannot have active acute or chronic graft versus host disease (GvHD)

          -  To be performed within 14 days prior to day 1 of protocol therapy: absolute neutrophil
             count (ANC) >= 1,000/mm^3

               -  NOTE: Growth factor is not permitted within 7 days of ANC assessment unless
                  cytopenia is secondary to disease involvement

               -  Exception: Unless documented bone marrow involvement by lymphoma

          -  To be performed within 14 days prior to day 1 of protocol therapy: platelets >=
             30,000/mm^3 * NOTE: Platelet transfusions are not permitted within 7 days of platelet
             assessment unless cytopenia is secondary to disease involvement

             * Exception: Unless documented bone marrow involvement by lymphoma

          -  To be performed within 14 days prior to day 1 of protocol therapy: total bilirubin =<
             1.5 x upper limit of normal (ULN) (=< for Gilbert's syndrome or documented hepatic
             involvement by lymphoma)

          -  To be performed within 14 days prior to day 1 of protocol therapy: aspartate
             aminotransferase (AST) =< 3 x ULN * If hepatic involvement by lymphoma: AST =< 5 x ULN

          -  To be performed within 14 days prior to day 1 of protocol therapy: alanine
             aminotransferase (ALT) =< 3 x ULN

             * If hepatic involvement by lymphoma: ALT =< 5 x ULN

          -  To be performed within 14 days prior to day 1 of protocol therapy: creatinine
             clearance of >= 50 mL/min per 24 hour urine or the Cockcroft-Gault formula

          -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

             * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required

          -  Agreement by WOCBP and males of childbearing potential* to use an adequate method of
             birth control (hormonal contraception is inadequate) or abstain from heterosexual
             activity for the course of the study through 90 days after the last dose of protocol
             therapy * Childbearing potential defined as not being surgically sterilized (men and
             women) or have not been free from menses for > 1 year (women only)

        Exclusion Criteria:

          -  Bcl2 inhibitors

          -  Any systemic anti-lymphoma therapy, including monoclonal antibody within 28 days or 5
             half-lives (whichever is shorter) of initiating protocol therapy

          -  Radiation and/or surgery (except lymph node or other diagnostic biopsies) within 14
             days prior to day 1 of protocol therapy

          -  Short course systemic corticosteroids for disease control, improvement of performance
             status or non-cancer indication within 7 days prior to day 1 of protocol therapy;
             stable ongoing corticosteroid use (i.e. at least 30 days) up to an equivalent dose of
             20 mg of prednisone is permissible

          -  Strong or moderate CYP3A inhibitors within 3 days prior to day 1 of protocol therapy

          -  Strong or moderate CYP3A inducers within 7 days prior to day 1 of protocol therapy

          -  P-gp inhibitors within 7 days prior to day 1 of protocol therapy

          -  Narrow therapeutic index P-gp substrates within 7 days prior to day 1 of protocol
             therapy

          -  Any other investigational agent or used an investigational device within 21 days prior
             to day 1 of protocol therapy

          -  Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g.,
             gastric bypass surgery, gastrectomy)

          -  Active human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B
             virus (HBV); subjects who have an undetectable HIV viral load with CD4 > 200 and are
             on highly active antiretroviral therapy (HAART) medication are allowed; subjects who
             are positive for hepatitis B core antibody or hepatitis B surface antigen must have a
             negative polymerase chain reaction (PCR) result before enrollment; those who are PCR
             positive will be excluded; patients who have had hepatitis C but have finished
             treatment and are PCR negative will be allowed (testing to be done only in patients
             suspected of having infections or exposures)

          -  Concurrent malignancy requiring active therapy

          -  Known central nervous system or meningeal involvement (in the absence of symptoms,
             investigation into central nervous system involvement is not required)

          -  A history of prior significant toxicity, other than thrombocytopenia, from another
             Bcl-2 family protein inhibitor

          -  Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II
             to IV definitions

          -  Active infection requiring systemic therapy

          -  Unable to swallow capsules, has a partial or small bowel obstruction, or has a
             gastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowel
             resection with malabsorption)

          -  WOCBP: Pregnant or breastfeeding

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0
Time Frame:Up to 30 days post-treatment
Safety Issue:
Description:During the first 2 cycles, all grades of toxicity will be collected. After cycle 2, only the highest grade of any toxicity will be collected for each cycle during protocol treatment and for the period of safety follow-up after end of treatment.

Secondary Outcome Measures

Measure:Complete response rate (CR) defined using by Lugano Classification 2014
Time Frame:Up to 24 months
Safety Issue:
Description:Rates and 95% Clopper-Pearson binomial confidence interval (CI) will be calculated for overall response rate (patients that have confirmed CR or PR), as well as for CR rate. The response evaluation will be based on a Simon's Two-Stage Optimal design to distinguish a promising 30% response rate (alternative hypothesis) from a disappointing rate (null hypothesis) of 10%, at a one-sided type I error of 10% and a power of 80%.
Measure:Duration of response (DOR) assessed using Lugano Classification 2014
Time Frame:From the start of study treatment up to 24 months
Safety Issue:
Description:DOR will be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.
Measure:Progression-free survival (PFS)
Time Frame:From the start of study treatment up to 24 months
Safety Issue:
Description:PFS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error. Median progression-free survival and overall survival and their corresponding 95% CIs will be estimated.
Measure:Overall survival (OS)
Time Frame:From the start of study treatment up to 24 months
Safety Issue:
Description:OS to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error. Median progression-free survival and overall survival and their corresponding 95% CIs will be estimated.
Measure:Time to response (TTR) assessed by Lugano Classification 2014
Time Frame:From the start of study treatment up to 24 months
Safety Issue:
Description:TTR to be estimated using the product-limit method of Kaplan- Meier with the Greenwood estimator of standard error.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

October 29, 2019