B-cell Chronic Lymphocytic Leukemia, B-Cell Diffuse Lymphoma, B Cell Lymphoma, Burkitt Lymphoma, Diffuse Well-differentiated Lymphocytic Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Non-Hodgkin's Lymphoma, Small Lymphocytic Lymphoma, Waldenstrom Macroglobulinemia
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 determine the long-term safety of a fixed-dose, daily regimen of PCI-32765 PO in subjects with B cell lymphoma or chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL).
Interventions
DRUGPCI-32765
Dose based on parent protocol
Sponsors
Janssen Research & Development, LLC
Pharmacyclics LLC.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women with recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (NHL) according to WHO classification (including, but not limited to, CLL/SLL, Waldenström's macroglobulinemia \[WM\], mantle cell lymphoma \[MCL\], and diffuse large B cell lymphoma \[DLBCL) who have met requirements for roll over from their parent protocol and want to continue study drug. * Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for 1 month following the last dose with study drug. Post menopausal females (\>45 years old and without menses for \>1 year) and surgically sterilized females are exempt from this criterion. * Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential. * Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty * Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
Exclusion criteria
* A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk * Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection. * Lactating or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | 30 days after last dose of study drug, continue up to 6 months | Subjects were to receive ibrutinib once daily at the dose level the subject was receiving in the parent study until disease progression or unacceptable toxicity. The study included Screening, Treatment (from the first dose until study drug discontinuation), and Follow-up Phases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progressive Disease (PD) | 30 days after last dose of study drug, continue up to 6 months | A progressive disease confirmed by a CT scan. |
| Death Event | 30 days after last dose of study drug | All death events are due to AE, progressive disease, and other reasons. |
| Documented Responses | 30 days after last dose of study drug, continue up to 6 months | Investigator-assessed responses were summarized descriptively for subjects with CLL/SLL and listed for subjects with other NHLs based on the efficacy population. |
Countries
United States
Participant flow
Recruitment details
27 July 2010 (the first Patient enrolled) to 31 March 2016 (the Last patient enrolled), Study was approved on June 2010.
Pre-assignment details
This study was open to subjects from prior ibrutinib studies who met eligibility criteria for rollover from their parent study and wanted to continue receiving study drug.
Participants by arm
| Arm | Count |
|---|---|
| A Long-term Safety Study of Bruton's Tyrosine Kinase (Btk) Inh A Long-term Safety Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia. This is a multicenter(16 sites in the USA), open-label, monotherapy, long-term extension study designed to evaluate the long-term (\> 6 months) safety and tolerability of a fixed daily dosing regimen of ibrutinib. Ibrutinib was supplied as 140 mg or 40 mg capsules for oral administration. Subjects were to receive daily administration of a fixed dose of ibrutinib at the same dose level as in the parent study (up to 840 mg). | 199 |
| Total | 199 |
Baseline characteristics
| Characteristic | A Long-term Safety Study of Bruton's Tyrosine Kinase (Btk) Inh |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 116 Participants |
| Age, Categorical Between 18 and 65 years | 83 Participants |
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 8.98 |
| Estimated creatinine clearance rate (mL/min) | 85.55 ML/min STANDARD_DEVIATION 34.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 185 Participants |
| Region of Enrollment United States | 199 participants |
| Sex: Female, Male Female | 56 Participants |
| Sex: Female, Male Male | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 111 / 199 |
| other Total, other adverse events | 114 / 199 |
| serious Total, serious adverse events | 111 / 199 |
Outcome results
Primary
Number of Subjects With Adverse Events
Subjects were to receive ibrutinib once daily at the dose level the subject was receiving in the parent study until disease progression or unacceptable toxicity. The study included Screening, Treatment (from the first dose until study drug discontinuation), and Follow-up Phases.
Time frame: 30 days after last dose of study drug, continue up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Number of Subjects With Adverse Events | 199 Participants |
Secondary
Death Event
All death events are due to AE, progressive disease, and other reasons.
Time frame: 30 days after last dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Death Event | 42 Participants |
Secondary
Documented Responses
Investigator-assessed responses were summarized descriptively for subjects with CLL/SLL and listed for subjects with other NHLs based on the efficacy population.
Time frame: 30 days after last dose of study drug, continue up to 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Documented Responses | CLL/SLL | 180 Participants |
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Documented Responses | Other NHL | 16 Participants |
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Documented Responses | Treatment discontinuation | 3 Participants |
Secondary
Progressive Disease (PD)
A progressive disease confirmed by a CT scan.
Time frame: 30 days after last dose of study drug, continue up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A LONG-TERM SAFETY STUDY OF BRUTON'S TYROSINE KINASE (BTK) INH | Progressive Disease (PD) | 70 Participants |