Trial Outcomes & Findings for Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL) (NCT NCT01292135)
NCT ID: NCT01292135
Last Updated: 2014-07-24
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Results posted on
2014-07-24
Participant Flow
Participant milestones
| Measure |
PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)
PCI-32765: 420 mg daily
FCR:
* Rituximab: 375 mg/m2 on Day 1 of Cycle 1 and a dose of 500 mg/m2 on Day 1(Cycle 2 to Cycle 6).
* Fludarabine: 25 mg/m2/day for 3 days (Days 1 to 3) of each cycle
* Cyclophosphamide: 250 mg/m2/day for 3 days (Days 1 to 3) of each cycle (Up to 6 Cycle)
|
PCI-32765 Plus Bendamustine/Rituximab (BR)
PCI-32765: 420 mg daily
BR:
* Rituximab: 375 mg/m2 on Day 1 of Cycle 1 and a dose of 500 mg/m2 on Day 1 (Cycle 2 to Cycle 6).
* Bendamustine; 70 mg/m² on Day 1 and 2 of each cycle (Up to 6 Cycles)
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
30
|
|
Overall Study
COMPLETED
|
3
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.3 Years
STANDARD_DEVIATION 1.53 • n=5 Participants
|
61.3 Years
STANDARD_DEVIATION 9.58 • n=7 Participants
|
60.8 Years
STANDARD_DEVIATION 9.24 • n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
30 participants
n=7 Participants
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.Population: The FCR arm was discontinued due to very limited use of this chemo regimen in this setting, statistical analysis were limited due to the small numbers of subjects in this treatment arm.
Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Incidence of Prolonged Hematologic Toxicity Started in Cycle 1
|
0 Percentage of Participants
Interval 0.0 to 11.6
|
0 Percentage of Participants
Dispersion not calculated due to small sample size n=3.
|
SECONDARY outcome
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
|
53.3 Percentage of Participants
|
33.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
|
66.7 Percentage of Participants
|
0 Percentage of Participants
|
SECONDARY outcome
Timeframe: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Overall Incidence of Serious Adverse Events (SAEs)
|
20 Percentage of Participants
|
33.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. Assessment of response to treatment will be done every 2 cycles for the first 6 months and then every 3 months thereafter until disease progression or prior to the administration of a new anticancer therapy and at follow-up visits.
Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])
|
93.3 Percentage of Participants
Interval 77.9 to 99.2
|
100 Percentage of Participants
Dispersion not calculated due to small sample size n=3.
|
SECONDARY outcome
Timeframe: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.Population: No participants in the FCR group had neutropenia, anemia or thrombocytopenia at baseline.
Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
PCI-32765: 420 mg daily
|
|---|---|---|
|
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
|
76.2 Percentage of Participants
Interval 52.8 to 91.8
|
—
|
SECONDARY outcome
Timeframe: From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest.Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.
Outcome measures
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 Participants
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
n=3 Participants
PCI-32765: 420 mg daily
|
|---|---|---|
|
Progression Free Survival Rate at 12 Months
|
85.9 Percentage of Participants
Interval 66.7 to 94.5
|
100 Percentage of Participants
Interval 100.0 to 100.0
|
Adverse Events
PCI-32765 Plus Bendamustine/Rituximab (BR)
Serious events: 6 serious events
Other events: 30 other events
Deaths: 0 deaths
PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 participants at risk
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)
n=3 participants at risk
PCI-32765: 420 mg daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.7%
2/30
|
0.00%
0/3
|
|
Infections and infestations
Cellulitis
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Dehydration
|
3.3%
1/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
3.3%
1/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/30
|
33.3%
1/3
|
|
Infections and infestations
Viral Infection
|
0.00%
0/30
|
33.3%
1/3
|
Other adverse events
| Measure |
PCI-32765 Plus Bendamustine/Rituximab (BR)
n=30 participants at risk
PCI-32765: 420 mg daily
|
PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)
n=3 participants at risk
PCI-32765: 420 mg daily
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
40.0%
12/30
|
33.3%
1/3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.7%
5/30
|
66.7%
2/3
|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
2/30
|
66.7%
2/3
|
|
Eye disorders
Conjuctivitis
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
70.0%
21/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Nausea
|
66.7%
20/30
|
66.7%
2/3
|
|
Gastrointestinal disorders
Constipation
|
30.0%
9/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
30.0%
9/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
20.0%
6/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Abdominal discomfort
|
13.3%
4/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dry mouth
|
13.3%
4/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Stomatitis
|
13.3%
4/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal distension
|
10.0%
3/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
3/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Mouth ulceration
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Tongue ulcerlation
|
6.7%
2/30
|
0.00%
0/3
|
|
General disorders
Fatigue
|
46.7%
14/30
|
0.00%
0/3
|
|
General disorders
Oedema peripheral
|
33.3%
10/30
|
0.00%
0/3
|
|
General disorders
Pyrexia
|
23.3%
7/30
|
0.00%
0/3
|
|
General disorders
Chills
|
16.7%
5/30
|
0.00%
0/3
|
|
General disorders
Asthenia
|
10.0%
3/30
|
0.00%
0/3
|
|
General disorders
Pain
|
10.0%
3/30
|
0.00%
0/3
|
|
General disorders
Chest discomfort
|
6.7%
2/30
|
0.00%
0/3
|
|
General disorders
Impaired healing
|
6.7%
2/30
|
33.3%
1/3
|
|
Immune system disorders
Drug hypersensitivity
|
6.7%
2/30
|
0.00%
0/3
|
|
Immune system disorders
Seasonal allergy
|
10.0%
3/30
|
0.00%
0/3
|
|
Infections and infestations
Upper respiratory tract infection
|
36.7%
11/30
|
33.3%
1/3
|
|
Infections and infestations
Sinusitis
|
26.7%
8/30
|
0.00%
0/3
|
|
Infections and infestations
Urinary tract infection
|
13.3%
4/30
|
0.00%
0/3
|
|
Infections and infestations
Cellulitis
|
6.7%
2/30
|
0.00%
0/3
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
2/30
|
0.00%
0/3
|
|
Infections and infestations
Pneomonia
|
6.7%
2/30
|
33.3%
1/3
|
|
Injury, poisoning and procedural complications
Contusion
|
20.0%
6/30
|
0.00%
0/3
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
10.0%
3/30
|
0.00%
0/3
|
|
Investigations
Weight decreased
|
10.0%
3/30
|
0.00%
0/3
|
|
Investigations
Blood uric acid increased
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
5/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
13.3%
4/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
13.3%
4/30
|
66.7%
2/3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.0%
3/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
10.0%
3/30
|
100.0%
3/3
|
|
Metabolism and nutrition disorders
Fluid retention
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.7%
2/30
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
26.7%
8/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
23.3%
7/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
5/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
5/30
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.0%
3/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
3/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.7%
2/30
|
0.00%
0/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
20.0%
6/30
|
0.00%
0/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
6.7%
2/30
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
30.0%
9/30
|
0.00%
0/3
|
|
Nervous system disorders
Dizziness
|
23.3%
7/30
|
0.00%
0/3
|
|
Nervous system disorders
Paraesthesia
|
6.7%
2/30
|
0.00%
0/3
|
|
Nervous system disorders
Syncope
|
6.7%
2/30
|
0.00%
0/3
|
|
Psychiatric disorders
Insomnia
|
23.3%
7/30
|
0.00%
0/3
|
|
Psychiatric disorders
Depression
|
6.7%
2/30
|
0.00%
0/3
|
|
Renal and urinary disorders
Haematuria
|
10.0%
3/30
|
0.00%
0/3
|
|
Renal and urinary disorders
Pollakiuria
|
10.0%
3/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
4/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
13.3%
4/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
10.0%
3/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
2/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash maculo papular
|
16.7%
5/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
13.3%
4/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
3/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Sunburn
|
6.7%
2/30
|
0.00%
0/3
|
|
Vascular disorders
Flushing
|
6.7%
2/30
|
0.00%
0/3
|
|
Vascular disorders
Hypotension
|
6.7%
2/30
|
0.00%
0/3
|
|
Infections and infestations
Oral herpes
|
0.00%
0/30
|
33.3%
1/3
|
|
Infections and infestations
Rhinitis
|
3.3%
1/30
|
33.3%
1/3
|
|
Infections and infestations
Skin Infection
|
0.00%
0/30
|
33.3%
1/3
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.3%
1/30
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/30
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/30
|
33.3%
1/3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place