B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
PCI-32765, Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Bruton's Tyrosine Kinase
Brief summary
The purpose of this study is to establish the safety and efficacy of orally administered PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.
Interventions
DRUGPCI-32765
420 mg daily or 840 mg daily
Sponsors
Pharmacyclics LLC.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. FOR TREATMENT-NAIVE GROUP ONLY: Men and women ≥ 65 years of age with confirmed diagnosis of CLL/SLL, who require treatment per NCI or International Working Group guidelines 15-18 2. FOR RELAPSED/REFRACTORY GROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL following previous therapy(ie, failed ≥ 2 previous treatments for CLL/SLL and at least 1 regimen had to have had a purine analog \[eg, fludarabine\] for subjects with CLL) 3. FOR HIGH-RISK RELAPSED/ REFRACTORYGROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL with suboptimal response to chemoimmunotherapy, defined as progression of disease within 24 months of initiation of a regimen containing at least a nucleoside analogue or bendamustine in combination with a monoclonal antibody or failure to respond to such a regimen. (Note: a minimum of 2 cycles of chemoimmunotherapy required for eligibility) 4. ECOG performance status of ≤ 2 5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
Exclusion criteria
1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to \< 2 years 2. Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration) 3. Central nervous system (CNS) involvement by lymphoma 4. Major surgery within 4 weeks before first dose of study drug 5. Concomitant use of medicines known to cause QT prolongation or torsades de pointes 6. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc \> 470 msec 7. Lactating or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) | From first dose to within 30 days of last dose of PCI-32765 | Number of participants who had experienced at least one treatment emergent AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Food Effect Cohort Assessments | Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design. | Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose. |
| Progression Free Survival Rate at 24 Months | The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months). | 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. |
| Percentage of Participants Achieving Response | The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 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. |
Countries
United States
Participant flow
Recruitment details
There are total 133 subjects enrolled however one subject never received treatment. Therefore, number of subjects Started the study is listed as 132 subjects.
Participants by arm
| Arm | Count |
|---|---|
| PCI-32765 PCI-32765: 420 mg daily or 840 mg daily | 116 |
| Food Effect Cohort PCI-32765: 420 mg daily | 16 |
| Total | 132 |
Baseline characteristics
| Characteristic | PCI-32765 | Food Effect Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 74 Participants | 7 Participants | 81 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 9 Participants | 51 Participants |
| Sex: Female, Male Female | 32 Participants | 2 Participants | 34 Participants |
| Sex: Female, Male Male | 84 Participants | 14 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 116 / 116 | 16 / 16 |
| serious Total, serious adverse events | 61 / 116 | 7 / 16 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (AEs)
Number of participants who had experienced at least one treatment emergent AEs.
Time frame: From first dose to within 30 days of last dose of PCI-32765
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI-32765 | Number of Participants With Treatment Emergent Adverse Events (AEs) | 116 Participants |
| Food Effect | Number of Participants With Treatment Emergent Adverse Events (AEs) | 11 Participants |
Secondary
Food Effect Cohort Assessments
Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose.
Time frame: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.
Population: Note: 16 subjects were participated in food effect cohort. However, the PK parameters for 1 subject under Fasted treatment period cannot be reliably estimated. The data for this subject were excluded from Fed/Fasted comparison.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI-32765 | Food Effect Cohort Assessments | 1.65 |
Secondary
Percentage of Participants Achieving Response
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.
Time frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI-32765 | Percentage of Participants Achieving Response | 71 Percentage of Participants |
| Food Effect | Percentage of Participants Achieving Response | 75.3 Percentage of Participants |
| Food- Effect | Percentage of Participants Achieving Response | 56.3 Percentage of Participants |
Secondary
Progression Free Survival Rate at 24 Months
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.
Time frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI-32765 | Progression Free Survival Rate at 24 Months | 96.3 Percentage of Participants |
| Food Effect | Progression Free Survival Rate at 24 Months | 73.6 Percentage of Participants |
| Food- Effect | Progression Free Survival Rate at 24 Months | NA Percentage of Participants |