Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Prolymphocytic

Leukemia, Prolymphocytic, T-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, T-Cell

T-cell Prolymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Venetoclax

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

Ibrutinib capsules taken orally once a day, 420 mg/day until the end-of-treatment.

ABBVIE INC.

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).

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.

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

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

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.

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.

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.

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.

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.

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.

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%.

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.

Participants eligible for autologous or allogeneic transplantation were transplant-naïve participants who achieved CR.

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.

AbbVie

Venetoclax + Ibrutinib

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Disease Duration

ECOG performance status was assessed as follows:

* 0: Fully active, able to carry on all predisease performance without restriction.
* 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
* 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
* 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
* 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Global Medical Services

The full analysis set includes all participants who received at least 1 dose of study drug (either venetoclax or ibrutinib).

Overall Response Rate (ORR)

Progression-Free Survival (PFS)

Full analysis set participants with a best overall response of CR, CRi, or PR

Duration of Response (DOR)

Time to Progression (TTP)

Event-free Survival (EFS)

Disease Control Rate (DCR)

Overall Survival (OS)

Participants who were transplant-naive and achieved CR. No participants achieved a CR to be eligible for transplant.

Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation

Any adverse event

AE with NCI-CTCAE toxicity Grade 3, 4, or 5

Serious adverse event

AE leading to venetoclax discontinuation, incl PD

AE leading to venetoclax interruption

AE leading to venetoclax reduction

AE with reasonable possibility related to venetoclax

AE leading to ibrutinib discontinuation, incl PD

AE leading to ibrutinib interruption

AE leading to ibrutinib reduction

AE with reasonable possibility related to ibrutinib

Serious AE with reasonable possibility related to venetoclax

Serious AE with reasonable possibility related to ibrutinib

AE leading to death

All deaths

All participants who received at least 1 dose of study drug (either venetoclax or ibrutinib)

Spots Global Cancer Trial Database for A Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Participants With T-cell Prolymphocytic Leukemia

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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