A Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Participants With T-cell Prolymphocytic Leukemia

November 23, 2022 updated by: AbbVie

A Prospective, Open-Label, Single-Arm, Phase 2, Multicenter Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Subjects With T-Cell Prolymphocytic Leukemia

The main objective of this study is to evaluate the efficacy of the combination of venetoclax plus ibrutinib for treating adults with T-cell prolymphocytic leukemia (T-PLL).

Study Overview

Detailed Description

This study is planned as an adaptive 2-stage design as follows:

Stage 1: Enroll 14 participants with relapsed or refractory (R/R) T-PLL and move to Stage 2 if 4 or more participants meet protocol-specified response criteria. Response assessment will be performed on a continued basis until all 14 participants have enrolled into Stage 1 and have completed the Week 24 disease assessment.

Stage 2: Enroll up to an additional 23 participants.

The study was stopped after Stage 1. Stage 2 was not conducted.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Ctr /ID# 209554
    • Wien
      • Vienna, Wien, Austria, 1090
        • Medizinische Universitaet Wien /ID# 208497
    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00290
        • Helsinki University Hospital /ID# 208108
      • Paris, France, 75013
        • Hopital Pitie Salpetriere /ID# 208730
    • Auvergne-Rhone-Alpes
      • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
        • HCL - Hôpital Lyon Sud /ID# 208731
    • Hauts-de-France
      • Lille, Hauts-de-France, France, 59037
        • CHRU Lille - Hopital Claude Huriez /ID# 208726
      • Cologne, Germany, 50937
        • University Hospital Cologne /ID# 208834
      • Trieste, Italy, 34128
        • Azienda Sanitaria Universitaria Giuliano Isontina /ID# 211487
      • Eindhoven, Netherlands, 5631 BM
        • Maxima Medisch Centrum /ID# 207989
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen /ID# 207990
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust /ID# 211263
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Oxford University Hospitals NHS Foundation Trust /ID# 211264
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute /ID# 207728
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0001
        • Mayo Clinic - Rochester /ID# 207692
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center /ID# 207746

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adequate liver, kidney and hematology function per laboratory values as described in the protocol.
  • Diagnosis of T-cell prolymphocytic leukemia (T-PLL) that requires treatment.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • Received prior alemtuzumab (unless unsuitable or unavailable).
  • Has no malignancies other than T-PLL that:

    • currently require systemic therapies;
    • were not previously treated with curative intention (unless the malignant disease is in a stable remission due to the discretion of the treating physician); or
    • developed signs of progression after curative treatment.

Exclusion Criteria:

  • History of or current decompensated cirrhosis including Child-Pugh class B or C, ascites, hepatic encephalopathy, or variceal bleeding.
  • Has human T-cell lymphotropic virus, type 1.
  • Prior allogeneic stem cell transplant within 6 months of study drug administration and requirement for graft versus host therapy.
  • Has an uncontrolled or active infection including severe acute respiratory syndrome- coronavirus-2 (SARS-COV-2).
  • Previously treated with a B-cell lymphoma (BCL)-2 inhibitor.
  • Received a prohibited therapy within the specified time frame as described in the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venetoclax + Ibrutinib
Participants received 400 mg venetoclax orally once a day after a 5-day ramp-up and 420 mg ibrutinib orally once a day for up to 2 years or until progressive disease, intolerability, or they became eligible for stem cell transplantation after achieving complete remission.
Venetoclax tablets taken orally once a day (QD). Initially, venetoclax was administered utilizing a 5-step dose ramp-up over 5 days. Subjects were hospitalized and closely monitored for 7 days. The venetoclax ramp-up was administered in a daily manner: 20 mg on Week 1 Day 1, 50 mg on Week 1 Day 2, 100 mg on Week 1 Day 3, 200 mg on Week 1 Day 4, and 400 mg on Week 1 Day 5 and thereafter, once daily, until the end-of-treatment. The dose of venetoclax may have been increased to 600 mg QD at Week 8 or thereafter.
Other Names:
  • ABT-199
  • GDC-0199
  • Venclexta®
  • Venclyxto®
Ibrutinib capsules taken orally once a day, 420 mg/day until the end-of-treatment.
Other Names:
  • Imbruvica®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment

ORR is defined as the percentage of participants achieving complete remission (CR), CR with incomplete bone marrow recovery (CRi), or partial remission (PR) as their best response per investigator assessment based on the T-PLL consensus criteria 2019.

CR: All of the following response criteria must be met:

Group A:

  • all lymph nodes < 1 cm;
  • spleen < 13 cm;
  • no constitutional symptoms;
  • circulating lymphocyte count < 4 × 10^9/L;
  • bone marrow T-PLL cells < 5% of mononuclear cells;
  • no other specific site involvement

Group B:

  • platelets ≥ 100 × 10^9 /L;
  • hemoglobin ≥ 11.0 g/dL;
  • neutrophils ≥ 1.5 × 10^9 /L.

CRi: All of the CR response criteria in Group A met; at least 1 parameter in Group B not achieved, unrelated to T-PLL, but related to drug toxicity.

PR: At least 2 of the parameters in Group A and 1 parameter in Group B need to improve if previously abnormal. If only 1 parameter of both Groups A and B is abnormal prior to therapy, only 1 parameter needs to improve.

Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.

Progression-free survival is defined as the time from the date of first dose of any study drug to the date of earliest disease progression or death. PFS was calculated using Kaplan-Meier methods.

Response was assessed by the investigator based on the T-PLL consensus criteria 2019.

Progressive disease (PD) is defined as meeting at least one of the criteria of Group A or Group B below:

Group A:

  • lymph nodes increase in > 20% in sum of long-axis diameters of up to 3 target lesions (SLD) from nadir;
  • spleen increase ≥ 50% in vertical length beyond normal from baseline;
  • circulating lymphocyte count increase ≥ 50% from baseline;
  • appearance of a new lesion;

Group B:

  • platelet count decrease of ≥ 50% from baseline due to T-PLL (not due to drug toxicity);
  • hemoglobin decrease of ≥ 2 g/dL from baseline due to T-PLL;
  • neutrophils decrease of ≥ 50% from baseline due to T-PLL.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Duration of Response (DOR)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.

Duration of response is defined for participants who achieved a best overall response of CR, CRi, or PR as the time from the date of first response (CR, CRi, or PR) to the earliest date of disease progression or death. DOR was calculated using Kaplan-Meier methods.

Response was assessed by the investigator based on the T-PLL consensus criteria 2019.

Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below:

Group A:

  • lymph nodes increase in > 20% in SLD from nadir;
  • spleen increase ≥ 50% in vertical length beyond normal from baseline;
  • circulating lymphocyte count increase ≥ 50% from baseline;
  • appearance of a new lesion;

Group B:

  • platelet count decrease of ≥ 50% from baseline due to T-PLL (not due to drug toxicity);
  • hemoglobin decrease of ≥ 2 g/dL from baseline due to T-PLL;
  • neutrophils decrease of ≥ 50% from baseline due to T-PLL.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Time to Progression (TTP)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.

Time to progression is defined as the time from the date of the participant's first dose of any study drug to the date of earliest disease progression. TTP was calculated using Kaplan-Meier methods.

Clinical response (laboratory and physical examination assessments) was assessed by the investigator according to the T-PLL consensus criteria 2019.

Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below:

Group A:

  • lymph nodes increase in > 20% in SLD from nadir;
  • spleen increase ≥ 50% in vertical length beyond normal from baseline;
  • circulating lymphocyte count increase ≥ 50% from baseline;
  • appearance of a new lesion;

Group B:

  • platelet count decrease of ≥ 50% from baseline due to T-PLL (not due to drug toxicity);
  • hemoglobin decrease of ≥ 2 g/dL from baseline due to T-PLL;
  • neutrophils decrease of ≥ 50% from baseline due to T-PLL.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Event-free Survival (EFS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.

Event-free survival is defined as time from participant's first dose of any study drug to the date of earliest disease progression, death, or start of a new anti-T-PLL therapy. EFS was calculated using Kaplan-Meier methods.

Clinical response (laboratory and physical examination assessments) was assessed by the investigator according to the T-PLL consensus criteria 2019.

Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below:

Group A:

  • lymph nodes increase in > 20% in SLD from nadir;
  • spleen increase ≥ 50% in vertical length beyond normal from baseline;
  • circulating lymphocyte count increase ≥ 50% from baseline;
  • appearance of a new lesion;

Group B:

  • platelet count decrease of ≥ 50% from baseline due to T-PLL (not due to drug toxicity);
  • hemoglobin decrease of ≥ 2 g/dL from baseline due to T-PLL;
  • neutrophils decrease of ≥ 50% from baseline due to T-PLL.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Disease Control Rate (DCR)
Time Frame: Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment

DCR is defined as the percentage of participants who achieved CR, CRi, PR, or stable disease (SD) as best overall response per investigator assessment based on the T-PLL consensus criteria 2019.

Stable disease is defined as meeting all of the following criteria for at least 3 months:

  • lymph nodes change of -29% to +20% in SLD;
  • spleen change of -49% to +49% beyond normal from baseline;
  • circulating lymphocyte count > 30 × 10^9 /L or change of -49% to +49%;
  • platelet count change of -49% to +49%;
  • hemoglobin < 11.0 g/dL or change < 50% from baseline or change < 2 g/dL;
  • neutrophils change of -49% to +49%.
Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment
Overall Survival (OS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
Overall survival is defined as the time from the date of the participant's first dose of any study drug to death from any cause. OS was calculated using Kaplan-Meier methods.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
Participants eligible for autologous or allogeneic transplantation were transplant-naïve participants who achieved CR.
From first dose of study drug to end of study; median time on study was 30.1 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time Frame: From first dose of study drug up to 30 days after last dose; median time on treatment was 13.86 weeks (range 1.0 to 44.4 weeks)

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are any event with onset after the first dose of study drug and no more than 30 days after the last dose of study drug.

A serious AE was an event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or an important medical event requiring medical or surgical intervention to prevent a serious outcome.

The Investigator rated the severity of each AE according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening and grade 5 = death.

The Investigator assessed the relationship of the AE to the use of study drug.

From first dose of study drug up to 30 days after last dose; median time on treatment was 13.86 weeks (range 1.0 to 44.4 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 14, 2020

Primary Completion (Actual)

November 4, 2021

Study Completion (Actual)

November 4, 2021

Study Registration Dates

First Submitted

March 12, 2019

First Submitted That Met QC Criteria

March 12, 2019

First Posted (Actual)

March 13, 2019

Study Record Updates

Last Update Posted (Actual)

December 19, 2022

Last Update Submitted That Met QC Criteria

November 23, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

IPD Sharing Time Frame

For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

IPD Sharing Access Criteria

Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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