Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL
Brief summary
The main objective of this study is to determine the progression free survival of umbralisib in participants who were intolerant to prior BTK (Bruton Tyrosine Kinase) inhibitors (ibrutinib, ACP-196, other) or prior PI3K-delta inhibitors (idelalisib, duvelisib, other).
Interventions
DRUGUmbralisib
Umbralisib was administered as a tablet(s), orally once daily.
Sponsors
TG Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL) * Discontinuation on prior BTK inhibitor or PI3K delta inhibitor due to adverse events within prior 9 months * Presence of measurable disease
Exclusion criteria
* Progression on prior BTK or PI3K delta inhibitor * Prior treatment with TGR-1202 * Richter's transformation or CLL transformation to aggressive lymphoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From Day 1 to the earlier of the first documentation of definitive disease progression or death (Up to 61.7 months) | PFS was defined as the interval from Day 1 to the earlier of the first documentation of definitive disease progression (PD) or death from any cause. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 61.7 months | ORR=percent of participants who achieve complete response (CR), or partial response (PR). |
| Time to Treatment Failure (TTF) | From Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death (up to approximately 61.7 months) | TTF is defined as a composite endpoint measuring time from Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. Estimates of median TTF was made using Kaplan-Meier methods. |
| Duration of Response (DOR) | From first documentation of CR or PR till disease progression/death (up to approximately 61.7 months) | DOR defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. Estimates of median DOR was made using Kaplan-Meier methods. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE's) as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) | From first dose of study treatment up to end of study (up to 61.7 months) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related. TEAEs included both serious and non-serious TEAEs. |
Countries
United States
Participant flow
Recruitment details
A total of 51 participants took part in the study at 15 investigative sites in the United States, from 21 April 2016 to 10 June 2021.
Participants by arm
| Arm | Count |
|---|---|
| Umbralisib Participants received 800 mg of umbralisib, orally, once daily until disease progression, unacceptable toxicity or the end of the study for 60.7 months.
Umbralisib: Umbralisib was administered as a tablet(s), orally once daily. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Death | 3 |
| Overall Study | Disease Progression | 25 |
| Overall Study | Investigator's Decision | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Non-compliance with Study | 1 |
| Overall Study | Reason Not Specified | 1 |
| Overall Study | Sponsor Discontinuation of the Study | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Umbralisib |
|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 10.13 |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized White | 48 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 51 |
| other Total, other adverse events | 51 / 51 |
| serious Total, serious adverse events | 22 / 51 |
Outcome results
Primary
Progression-free Survival
PFS was defined as the interval from Day 1 to the earlier of the first documentation of definitive disease progression (PD) or death from any cause. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment.
Time frame: From Day 1 to the earlier of the first documentation of definitive disease progression or death (Up to 61.7 months)
Population: The modified Intent to Treat (mITT) population included all participants who were treated with study drug and provided at least one efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Umbralisib | Progression-free Survival | 19.7 months |
Secondary
Duration of Response (DOR)
DOR defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. Estimates of median DOR was made using Kaplan-Meier methods.
Time frame: From first documentation of CR or PR till disease progression/death (up to approximately 61.7 months)
Population: The mITT population included all participants who were treated with study drug and provided at least one efficacy assessment. Here, Overall number of participants analyzed signifies those who have documented CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Umbralisib | Duration of Response (DOR) | 19.4 months |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAE's) as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related. TEAEs included both serious and non-serious TEAEs.
Time frame: From first dose of study treatment up to end of study (up to 61.7 months)
Population: The safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Umbralisib | Number of Participants With Treatment-Emergent Adverse Events (TEAE's) as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) | 51 Participants |
Secondary
Overall Response Rate (ORR)
ORR=percent of participants who achieve complete response (CR), or partial response (PR).
Time frame: Up to 61.7 months
Population: The mITT population included all participants who were treated with study drug and provided at least one efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Umbralisib | Overall Response Rate (ORR) | 34 percentage of participants |
Secondary
Time to Treatment Failure (TTF)
TTF is defined as a composite endpoint measuring time from Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. Estimates of median TTF was made using Kaplan-Meier methods.
Time frame: From Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death (up to approximately 61.7 months)
Population: The mITT population included all participants who were treated with study drug and provided at least one efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Umbralisib | Time to Treatment Failure (TTF) | 13.6 months |