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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03873493
Registration number
NCT03873493
Ethics application status
Date submitted
12/03/2019
Date registered
13/03/2019
Date last updated
19/12/2022
Titles & IDs
Public title
A Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Participants With T-cell Prolymphocytic Leukemia
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Scientific title
A Prospective, Open-Label, Single-Arm, Phase 2, Multicenter Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Subjects With T-Cell Prolymphocytic Leukemia
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Secondary ID [1]
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2018-002179-17
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Secondary ID [2]
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M18-803
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Leukemia
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T-cell Prolymphocytic Leukemia (T-PLL)
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Cancer
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Ibrutinib
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.
Treatment: Drugs: Venetoclax
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.
Treatment: Drugs: Ibrutinib
Ibrutinib capsules taken orally once a day, 420 mg/day until the end-of-treatment.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall Response Rate (ORR)
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Assessment method [1]
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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.
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Timepoint [1]
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Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment
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Secondary outcome [1]
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Progression-Free Survival (PFS)
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Assessment method [1]
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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.
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Timepoint [1]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [2]
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Duration of Response (DOR)
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Assessment method [2]
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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.
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Timepoint [2]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [3]
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Time to Progression (TTP)
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Assessment method [3]
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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.
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Timepoint [3]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [4]
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Event-free Survival (EFS)
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Assessment method [4]
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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.
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Timepoint [4]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [5]
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Disease Control Rate (DCR)
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Assessment method [5]
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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%.
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Timepoint [5]
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Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment
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Secondary outcome [6]
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Overall Survival (OS)
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Assessment method [6]
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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.
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Timepoint [6]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [7]
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Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation
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Assessment method [7]
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Participants eligible for autologous or allogeneic transplantation were transplant-naïve participants who achieved CR.
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Timepoint [7]
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From first dose of study drug to end of study; median time on study was 30.1 weeks.
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Secondary outcome [8]
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Number of Participants With Treatment-emergent Adverse Events (TEAE)
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Assessment method [8]
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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.
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Timepoint [8]
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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)
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
14/01/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
4/11/2021
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Sample size
Target
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Accrual to date
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Final
14
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Peter MacCallum Cancer Ctr /ID# 209554 - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Massachusetts
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Country [2]
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United States of America
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State/province [2]
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Minnesota
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United States of America
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State/province [3]
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Texas
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Austria
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State/province [4]
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Wien
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Country [5]
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Finland
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State/province [5]
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Uusimaa
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Country [6]
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France
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State/province [6]
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Auvergne-Rhone-Alpes
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Country [7]
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France
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State/province [7]
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Hauts-de-France
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Country [8]
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France
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State/province [8]
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Paris
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Country [9]
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Germany
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State/province [9]
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Cologne
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Country [10]
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Italy
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State/province [10]
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Trieste
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Netherlands
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Eindhoven
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Country [12]
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Netherlands
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State/province [12]
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Groningen
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Country [13]
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United Kingdom
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State/province [13]
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Oxfordshire
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Country [14]
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United Kingdom
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State/province [14]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
AbbVie
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03873493
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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ABBVIE INC.
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Address
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AbbVie
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Phone
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Fax
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Email
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Contact person for public queries
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Address
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03873493
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