Trial Outcomes & Findings for Phase 2 Study of the Combination of Bruton's Tyrosine Kinase Inhibitor PCI-32765 and Rituximab in High-Risk Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Patients (NCT NCT01520519)
NCT ID: NCT01520519
Last Updated: 2019-09-18
Results Overview
Progression free survival defined as the time interval from treatment to progressive disease or death, whichever happens earlier. Participants in complete remission (CR), partial remission (PR) or stable disease (SD) are all counted as progression-free. Survival or times to progression functions estimated using the Kaplan-Meier method.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
up to 50 months
Results posted on
2019-09-18
Participant Flow
Recruitment Details: February 2012 - September 2012
Participant milestones
| Measure |
Rituximab + PCI-32765
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 2 Study of the Combination of Bruton's Tyrosine Kinase Inhibitor PCI-32765 and Rituximab in High-Risk Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Patients
Baseline characteristics by cohort
| Measure |
Rituximab + PCI-32765
n=40 Participants
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
26 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
14 Participants
n=5 Participants
|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 50 monthsPopulation: 1 participant was not evaluable for response
Progression free survival defined as the time interval from treatment to progressive disease or death, whichever happens earlier. Participants in complete remission (CR), partial remission (PR) or stable disease (SD) are all counted as progression-free. Survival or times to progression functions estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Rituximab + PCI-32765
n=39 Participants
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
Progression Free Survival (PFS)
|
45 Months
Interval 2.0 to 50.0
|
PRIMARY outcome
Timeframe: 7 monthsPopulation: 1 participant was not evaluable for response
Over all Response = complete remission (CR) + partial remission (PR). Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; positive or negative minimal residual disease (MRD); Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts
Outcome measures
| Measure |
Rituximab + PCI-32765
n=39 Participants
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
Number of Participants With a Response
|
37 Participants
|
Adverse Events
Rituximab + PCI-32765
Serious events: 18 serious events
Other events: 40 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Rituximab + PCI-32765
n=40 participants at risk
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
General disorders
Abdominal Pain
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Cardiac disorders
Atrial fibrillation
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Cardiac disorders
Cardiac disorders - other
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Eye disorders
Eye disorders - other
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Renal and urinary disorders
Hematuria
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Nervous system disorders
Intracranial hemorrhage
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Infections and infestations
Lung Infection
|
22.5%
9/40 • Number of events 11 • 7 months
|
|
Infections and infestations
Mucosal infection
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - other
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
2.5%
1/40 • Number of events 1 • 7 months
|
|
Renal and urinary disorders
Renal and urinary disorders - other
|
2.5%
1/40 • Number of events 3 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - other
|
2.5%
1/40 • Number of events 2 • 7 months
|
|
Infections and infestations
Sepsis
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Infections and infestations
Wound Infection
|
2.5%
1/40 • Number of events 1 • 7 months
|
Other adverse events
| Measure |
Rituximab + PCI-32765
n=40 participants at risk
Rituximab (375 mg/m2) given intravenously (IV) on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6. PCI-32765 started on Day 2 of cycle 1 at a dose of 420 mg (3 \* 140-mg capsules) orally daily and will be continued daily.
Rituximab: 375 mg/m2 intravenously on Day 1, Day 8, Day 15, and Day 22, then continued once every 4 weeks only on Days 1 during cycles 2 - 6.
PCI-32765: 420 mg (3 \* 140-mg capsules) orally started on Day 2 of cycle 1 once daily and will be continued daily.
|
|---|---|
|
Infections and infestations
Lung Infection
|
27.5%
11/40 • Number of events 11 • 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
35.0%
14/40 • Number of events 14 • 7 months
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
10/40 • Number of events 10 • 7 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.0%
2/40 • Number of events 2 • 7 months
|
|
General disorders
Fatigue
|
17.5%
7/40 • Number of events 7 • 7 months
|
|
Gastrointestinal disorders
Nausea/vomiting
|
37.5%
15/40 • Number of events 15 • 7 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
27.5%
11/40 • Number of events 11 • 7 months
|
|
Blood and lymphatic system disorders
Bleeding event
|
32.5%
13/40 • Number of events 13 • 7 months
|
|
Nervous system disorders
Peripheral Neuropathy
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Investigations
Weight Gain
|
10.0%
4/40 • Number of events 4 • 7 months
|
|
Eye disorders
Eye disorders
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Gastrointestinal disorders
Mucositis
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.0%
2/40 • Number of events 2 • 7 months
|
|
Cardiac disorders
Atrial fibrillation
|
5.0%
2/40 • Number of events 2 • 7 months
|
|
Renal and urinary disorders
Urinary tract infection
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Psychiatric disorders
Insomnia
|
10.0%
4/40 • Number of events 4 • 7 months
|
|
General disorders
Headache
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Blood and lymphatic system disorders
Anemia
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Vascular disorders
Hot flashes
|
5.0%
2/40 • Number of events 2 • 7 months
|
|
Gastrointestinal disorders
Constipation
|
7.5%
3/40 • Number of events 3 • 7 months
|
|
Psychiatric disorders
Anxiety
|
5.0%
2/40 • Number of events 2 • 7 months
|
|
Gastrointestinal disorders
Dry Mouth
|
5.0%
2/40 • Number of events 2 • 7 months
|
Additional Information
Jan Burger MD./Professor
The University of Texas MD Anderson Cancer Center
Phone: 713-563-1487
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place