Trial Outcomes & Findings for Evaluate the Efficacy and Safety of TGR-1202 in Participants With Chronic Lymphocytic Leukemia Who Are Intolerant to Prior Therapy (NCT NCT02742090)
NCT ID: NCT02742090
Last Updated: 2024-07-03
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
51 participants
Primary outcome timeframe
From Day 1 to the earlier of the first documentation of definitive disease progression or death (Up to 61.7 months)
Results posted on
2024-07-03
Participant Flow
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.
Participant milestones
| Measure |
Umbralisib
Participants received 800 milligrams (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.
|
|---|---|
|
Overall Study
STARTED
|
51
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
51
|
Reasons for withdrawal
| Measure |
Umbralisib
Participants received 800 milligrams (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.
|
|---|---|
|
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
Sponsor Discontinuation of the Study
|
5
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Reason Not Specified
|
1
|
Baseline Characteristics
Evaluate the Efficacy and Safety of TGR-1202 in Participants With Chronic Lymphocytic Leukemia Who Are Intolerant to Prior Therapy
Baseline characteristics by cohort
| Measure |
Umbralisib
n=51 Participants
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.
|
|---|---|
|
Age, Continuous
|
69.3 years
STANDARD_DEVIATION 10.13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
48 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Umbralisib
n=47 Participants
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.
|
|---|---|
|
Progression-free Survival
|
19.7 months
Interval 12.9 to 24.8
|
SECONDARY outcome
Timeframe: Up to 61.7 monthsPopulation: The mITT population included all participants who were treated with study drug and provided at least one efficacy assessment.
ORR=percent of participants who achieve complete response (CR), or partial response (PR).
Outcome measures
| Measure |
Umbralisib
n=47 Participants
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.
|
|---|---|
|
Overall Response Rate (ORR)
|
34 percentage of participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Umbralisib
n=47 Participants
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.
|
|---|---|
|
Time to Treatment Failure (TTF)
|
13.6 months
Interval 9.4 to 19.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Umbralisib
n=16 Participants
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.
|
|---|---|
|
Duration of Response (DOR)
|
19.4 months
Interval 8.4 to
Upper limit of 95% CI was not estimable due to low number of participants.
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Umbralisib
n=51 Participants
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.
|
|---|---|
|
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
|
Adverse Events
Umbralisib
Serious events: 22 serious events
Other events: 51 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Umbralisib
n=51 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.9%
3/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Colitis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Pancreatitis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Pancreatitis acute
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
General disorders
Asthenia
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Immune system disorders
Hypersensitivity
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Influenza
|
3.9%
2/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Bronchitis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
COVID-19
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Cellulitis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Intervertebral discitis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Sepsis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Urinary tract infection bacterial
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Influenza A virus test positive
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Platelet count decreased
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Transaminases increased
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Urticaria
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Vascular disorders
Deep vein thrombosis
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Vascular disorders
Embolism
|
2.0%
1/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
Other adverse events
| Measure |
Umbralisib
n=51 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
70.6%
36/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
62.7%
32/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Constipation
|
17.6%
9/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
17.6%
9/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
9.8%
5/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
General disorders
Fatigue
|
23.5%
12/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
General disorders
Oedema peripheral
|
19.6%
10/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
General disorders
Pyrexia
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
17.6%
9/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Contusion
|
21.6%
11/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
19.6%
10/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Neutrophil count decreased
|
19.6%
10/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Alanine aminotransferase increased
|
17.6%
9/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Blood alkaline phosphatase increased
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Investigations
Platelet count decreased
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
19.6%
10/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.7%
8/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
9.8%
5/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
27.5%
14/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Dizziness
|
15.7%
8/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Paraesthesia
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Tremor
|
11.8%
6/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Psychiatric disorders
Insomnia
|
29.4%
15/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.7%
8/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.8%
5/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.7%
8/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
13.7%
7/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.8%
5/51 • From first dose of study treatment up to end of study (up to approximately 61.7 months)
The safety population included all participants who received at least one dose of study treatment.
|
Additional Information
TG Therapeutics Clinical Support Team
TG Therapeutics
Phone: 1-877-575-8489
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee PI is restricted from publication until after the multi-center paper is published.
- Publication restrictions are in place
Restriction type: OTHER