Trial Outcomes & Findings for Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL (NCT NCT01752426)
NCT ID: NCT01752426
Last Updated: 2020-02-24
Results Overview
Stable isotopic labeling with deuterated water (2\^H2O) to measure directly the effects of PCI-32765 (ibrutinib) on leukemia cell death in the peripheral blood of participants .
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
every three months, up to one year
Results posted on
2020-02-24
Participant Flow
Recruitment Period: December 2012 - June 2013
Participant milestones
| Measure |
Heavy Water + PCI-32765
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL
Baseline characteristics by cohort
| Measure |
Heavy Water + PCI-32765
n=30 Participants
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: every three months, up to one yearStable isotopic labeling with deuterated water (2\^H2O) to measure directly the effects of PCI-32765 (ibrutinib) on leukemia cell death in the peripheral blood of participants .
Outcome measures
| Measure |
Heavy Water + PCI-32765
n=30 Participants
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
|
|---|---|
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Change in Leukemia Cell Death
Daily death rate of blood cells before therapy
|
0.18 percentage of cell death
Interval 0.0 to 0.7
|
|
Change in Leukemia Cell Death
Daily death rate of blood cells after therapy
|
1.5 percentage of cell death
Interval 0.0 to 3.0
|
SECONDARY outcome
Timeframe: every three months, up to one yearMeasurement of the fraction of recently born versus older leukemia cells in the peripheral blood of participants before and during PCI-32765 therapy, to determine the effects of PCI-32765 (ibrutinib) therapy on the birth rates of the leukemia cells.
Outcome measures
| Measure |
Heavy Water + PCI-32765
n=30 Participants
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
|
|---|---|
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Percentage of Recently Born Leukemia Cells Mobilized Into the Blood by PCI-32765 Treatment
Daily cell birth rate before therapy
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0.39 percentage of leukemia cells
Interval 0.17 to 1.04
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|
Percentage of Recently Born Leukemia Cells Mobilized Into the Blood by PCI-32765 Treatment
Daily cell birth rate during therapy
|
0.05 percentage of leukemia cells
Interval 0.0 to 0.36
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Adverse Events
Heavy Water + PCI-32765
Serious events: 16 serious events
Other events: 30 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Heavy Water + PCI-32765
n=30 participants at risk
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
|
|---|---|
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Cardiac disorders
Atrial Fibrillation
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16.7%
5/30 • Number of events 6 • Monthly, for up to 1 year
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Vascular disorders
Hematoma
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Infections and infestations
Lung Infection
|
3.3%
1/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Cardiac disorders
Mobitz (tyep)II atrioventricular block
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Infections and infestations
Nail Infection
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified
|
6.7%
2/30 • Number of events 2 • Monthly, for up to 1 year
|
|
General disorders
Pain Extremity
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Cardiac disorders
Pericardial effusion
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Infections and infestations
Sinusitis
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusions
|
10.0%
3/30 • Number of events 3 • Monthly, for up to 1 year
|
|
Infections and infestations
Skin infection
|
3.3%
1/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Psychiatric disorders
Suicide attempt
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
|
Nervous system disorders
Syncope
|
3.3%
1/30 • Number of events 1 • Monthly, for up to 1 year
|
Other adverse events
| Measure |
Heavy Water + PCI-32765
n=30 participants at risk
50ml 70% 2\^H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (\~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
23.3%
7/30 • Number of events 7 • Monthly, for up to 1 year
|
|
Cardiac disorders
Cardiac Disorders other
|
33.3%
10/30 • Number of events 12 • Monthly, for up to 1 year
|
|
Gastrointestinal disorders
Gastrointestinal other
|
33.3%
10/30 • Number of events 10 • Monthly, for up to 1 year
|
|
Vascular disorders
Hypertension
|
30.0%
9/30 • Number of events 9 • Monthly, for up to 1 year
|
|
Infections and infestations
Infection
|
16.7%
5/30 • Number of events 5 • Monthly, for up to 1 year
|
|
Gastrointestinal disorders
Oral Mucositis
|
23.3%
7/30 • Number of events 7 • Monthly, for up to 1 year
|
|
General disorders
Pain
|
76.7%
23/30 • Number of events 26 • Monthly, for up to 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.7%
2/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Gastrointestinal disorders
Anorexia
|
10.0%
3/30 • Number of events 3 • Monthly, for up to 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
20.0%
6/30 • Number of events 6 • Monthly, for up to 1 year
|
|
General disorders
Bruising
|
46.7%
14/30 • Number of events 14 • Monthly, for up to 1 year
|
|
General disorders
Diarrhea
|
53.3%
16/30 • Number of events 16 • Monthly, for up to 1 year
|
|
Nervous system disorders
Dizziness
|
43.3%
13/30 • Number of events 13 • Monthly, for up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspena
|
13.3%
4/30 • Number of events 4 • Monthly, for up to 1 year
|
|
General disorders
Edema
|
43.3%
13/30 • Number of events 13 • Monthly, for up to 1 year
|
|
General disorders
Fatigue
|
70.0%
21/30 • Number of events 21 • Monthly, for up to 1 year
|
|
Renal and urinary disorders
Hematuria
|
6.7%
2/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
26.7%
8/30 • Number of events 8 • Monthly, for up to 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
6.7%
2/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
6.7%
2/30 • Number of events 2 • Monthly, for up to 1 year
|
|
Skin and subcutaneous tissue disorders
Skin other
|
23.3%
7/30 • Number of events 7 • Monthly, for up to 1 year
|
|
Skin and subcutaneous tissue disorders
Skin rash
|
36.7%
11/30 • Number of events 11 • Monthly, for up to 1 year
|
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