Trial Outcomes & Findings for A Study of ABT-199 Plus Ibrutinib and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (NCT NCT03136497)
NCT ID: NCT03136497
Last Updated: 2024-09-23
Results Overview
Define maximum tolerated dose and /or recommended phase II dose for the combinations of venetoclax (ABT-199, GDC-0199) plus Ibrutinib (PCI-32765) and rituximab in Relapsed or Refractory DLBCL by assessing the incidence of dose limiting toxicities (DLTs).
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
10 participants
Primary outcome timeframe
29 days
Results posted on
2024-09-23
Participant Flow
10 Patients Consented (9 started, 1 screen failure)
Participant milestones
| Measure |
400mg ABT-199
400mg ABT-199 Dose Level
|
800mg ABT-199
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
3
|
2
|
|
Overall Study
COMPLETED
|
4
|
3
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
400mg ABT-199
400mg ABT-199 Dose Level
|
800mg ABT-199
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Overall Study
Screen Failure
|
1
|
0
|
0
|
Baseline Characteristics
A Study of ABT-199 Plus Ibrutinib and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Baseline characteristics by cohort
| Measure |
400mg ABT-199
n=5 Participants
400mg ABT-199 Dose Level
|
800mg ABT-199
n=3 Participants
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 Participants
800mg ABT-199 Dose Level Expansion Arm
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Age, Continuous
|
70 Years
n=5 Participants
|
53 Years
n=7 Participants
|
84 Years
n=5 Participants
|
71.5 Years
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
10 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 29 daysDefine maximum tolerated dose and /or recommended phase II dose for the combinations of venetoclax (ABT-199, GDC-0199) plus Ibrutinib (PCI-32765) and rituximab in Relapsed or Refractory DLBCL by assessing the incidence of dose limiting toxicities (DLTs).
Outcome measures
| Measure |
ABT-199 Plus Ibrutinib and Rituximab
n=9 Participants
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
ABT-199: Oral dose daily until disease progression
Ibrutinib: Oral dose daily until disease progression
Rituximab: Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1
|
800mg ABT-199
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
800 mg
|
—
|
—
|
SECONDARY outcome
Timeframe: 36 MonthsPopulation: Number of participants with treatment-emergency adverse events
Adverse events will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
Outcome measures
| Measure |
ABT-199 Plus Ibrutinib and Rituximab
n=4 Participants
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
ABT-199: Oral dose daily until disease progression
Ibrutinib: Oral dose daily until disease progression
Rituximab: Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1
|
800mg ABT-199
n=3 Participants
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 Participants
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Incidence of Treatment-emergent Adverse Events.
|
3 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 MonthsPopulation: Median Progression Free Survival
The duration of PFS is defined as the time from the beginning of the first cycle of treatment to the date of progressive disease or death from any cause. PFS will be estimated using Kaplan-Meier method.
Outcome measures
| Measure |
ABT-199 Plus Ibrutinib and Rituximab
n=3 Participants
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
ABT-199: Oral dose daily until disease progression
Ibrutinib: Oral dose daily until disease progression
Rituximab: Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1
|
800mg ABT-199
n=2 Participants
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 Participants
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Efficacy as Assessed by Progression Free Survival (PFS)
|
2 Months
Interval 1.0 to 4.0
|
2 Months
Interval 2.0 to 2.0
|
2 Months
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: 36 MonthsPopulation: Median Overall Survival
The duration of OS is defined as the time from the beginning of the first cycle of treatment to the date of death from any cause. OS will be estimated using Kaplan-Meier method.
Outcome measures
| Measure |
ABT-199 Plus Ibrutinib and Rituximab
n=3 Participants
Cycle length will be 28 days. Venetoclax will be administered orally QD (Once Daily), continuously for 24 cycles. Ibrutinib will be administered orally QD, continuously for 24 cycles. Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1), Commercially available rituximab IV will be used.
ABT-199: Oral dose daily until disease progression
Ibrutinib: Oral dose daily until disease progression
Rituximab: Rituximab will be administered IV per institutional standards. weekly X 4 (Cycle 1); once on Day 1 of cycles 2-6 only, then every other cycle until Cycle 24 (total 18 doses of Rituxan from C1D1
|
800mg ABT-199
n=3 Participants
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 Participants
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Efficacy as Assessed by Overall Survival (OS)
|
8.6 Months
Interval 2.1 to 32.1
|
3.5 Months
Interval 2.1 to 11.2
|
9.4 Months
Interval 9.4 to 9.4
|
Adverse Events
400mg ABT-199
Serious events: 3 serious events
Other events: 3 other events
Deaths: 3 deaths
800mg ABT-199
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Dose-Expansion 800mg ABT-199
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
400mg ABT-199
n=4 participants at risk
400mg ABT-199 Dose Level
|
800mg ABT-199
n=3 participants at risk
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 participants at risk
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Gastrointestinal disorders
Hemorrhoidal Bleed
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Musculoskeletal and connective tissue disorders
Left Hip Pain
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Nervous system disorders
Syncopal Episode
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
Other adverse events
| Measure |
400mg ABT-199
n=4 participants at risk
400mg ABT-199 Dose Level
|
800mg ABT-199
n=3 participants at risk
800mg ABT-199 Dose Level
|
Dose-Expansion 800mg ABT-199
n=2 participants at risk
800mg ABT-199 Dose Level Expansion Arm
|
|---|---|---|---|
|
Investigations
Alk Phosphatase Elevated
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Respiratory, thoracic and mediastinal disorders
Allergies, seasonal
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
2/4 • Number of events 2 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Infections and infestations
Clostridium difficile
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Investigations
Elevated AST
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Gastrointestinal disorders
Gastric Upset (GERD)
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Nervous system disorders
Headaches
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Renal and urinary disorders
Hematuria
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
100.0%
2/2 • Number of events 2 • 36 Months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.0%
1/4 • Number of events 1 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
100.0%
2/2 • Number of events 2 • 36 Months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
25.0%
1/4 • Number of events 1 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Investigations
LDH Elevated
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
General disorders
Localized edema LLE
|
25.0%
1/4 • Number of events 1 • 36 Months
|
0.00%
0/3 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Gastrointestinal disorders
Loose Bowels
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • 36 Months
|
66.7%
2/3 • Number of events 2 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Blood and lymphatic system disorders
Neutropenia
|
50.0%
2/4 • Number of events 3 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/4 • 36 Months
|
33.3%
1/3 • Number of events 1 • 36 Months
|
0.00%
0/2 • 36 Months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Renal and urinary disorders
Urinary Incontinence
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Reproductive system and breast disorders
Vaginal Bleed
|
0.00%
0/4 • 36 Months
|
0.00%
0/3 • 36 Months
|
50.0%
1/2 • Number of events 1 • 36 Months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • 36 Months
|
66.7%
2/3 • Number of events 2 • 36 Months
|
0.00%
0/2 • 36 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place