The primary objective is to demonstrate the efficacy in subjects with R/R T-PLL treated with venetoclax plus ibrutinib.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the ORR which is defined as the proportion of subjects
achieving CR, CRi, or PR as their best response (per investigator assessment)
in R/R subjects.
Secondary outcome
Key secondary endpoints are as follows:
• PFS
• Duration of response
• Time-to-progression
• Overall survival
• Number of eligible subjects reaching autologous or allogeneic transplant
• Event-free survival
• Disease Control rate
Background summary
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid
malignancy characterized by proliferation of post-thymic prolymphocytes,
usually refractory to current treatment strategies or complicated by relapse
and associated with short overall survival. Thus far, alemtuzumab remains the
most effective treatment option in patients with T-PLL; however, despite
relatively high response rates (50% to 90%), all patients eventually relapse
with a median progression-free survival (PFS) of less than 12 months.
Allogeneic stem cell transplantation is considered a treatment goal for
eligible patients since long survival durations have been observed.
In 2 recent ex vivo drug screening studies, consistent activities of B-cell
lymphoma (BCL)-2 inhibition in T-PLL were observed. Venetoclax is a potent,
selective, and orally bioavailable small molecule inhibitor of BCL-2. However,
potential mechanisms of resistance may develop through BCL-2 and BCL-XL
induction. Ex vivo drug combination studies in primary T-PLL subject samples
demonstrated that T-PLL cell-specific synergism of venetoclax was highest with
ibrutinib.
Study objective
The primary objective is to demonstrate the efficacy in subjects with R/R T-PLL
treated with venetoclax plus ibrutinib.
Study design
This study is an open-label, single-arm, Phase 2, multicenter study evaluating
the efficacy of venetoclax plus ibrutinib.
Intervention
All subjects will receive venetoclax orally once daily (QD) plus Ibrutinib
dosed orally QD.
Study burden and risks
Effective treatment options remain dismal for patients with R/R T-PLL as well
as for treatment-naïve patients who have no access or are ineligible to
treatment with alemtuzumab. The recently reported ex vivo data and very limited
subject data provide rationale for a clinical study with the combination of
venetoclax and ibrutinib. Clinical data from this same combination target dose
regimen has also recently been presented for a different indication (i.e., CLL
[CAPTIVATE study]). Early data from 163 subjects show a spectrum of adverse
events (AEs) consistent with the historic safety profile of single-agent
ibrutinib and single-agent venetoclax with no new safety signals and promising
activity (77% undetectable minimal residual disease in peripheral blood after 6
months of therapy).
Subjects will be visiting the hospital more frequently and a 7-day
hospitalization is required during ramp-up of venetoclax. There will be more
frequent blood draws. Subjects will undergo CT-scans and a bone marrow biopsy
if a CT-scan indicates a CR/CRi. Subjects will be tested for hepatitis B, C,
HIV, pregnancy, and TLS and are asked to complete a dosing diary.
Knollstrasse -
Ludwigshafen 67061
DE
Knollstrasse -
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
- Male or female subjects, at least 18 years old, with a diagnosis of R/R T-PLL
that requires treatment and suitable for oral administration of study drugs.
- Subjects should meet the following disease activity criteria: an Eastern
Cooperative Oncology Group performance status <= 2.
- Subjects should have laboratory values meeting the following criteria:
• Alanine aminotransferase/aspartate aminotransferase <= 3 × the upper limit of
normal (ULN);
• Adequate liver function as indicated by a total bilirubin <= 1.5 x ULN
(subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN)
• Absolute neutrophil count > 1000/µL;
• Platelet count > 50,000/µL;
• Creatinine clearance >= 50 mL/minute; and
• Hemoglobin > 8 g/dL.
Exclusion criteria
-
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002179-17-NL |
| ClinicalTrials.gov | NCT03873493 |
| CCMO | NL70384.042.19 |