Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory/Relapsed Chronic Lymphocytic Leukemia
Conditions
Keywords
Bruton's Tyrosine Kinase, CLL, SLL, B-PLL
Brief summary
This is a Phase II, single institution open-label, non-randomized monotherapy study to evaluate the clinical efficacy and durable disease control of PCI-32765 administered to patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having deletion 17p13 independently evaluated.
Detailed description
This is a clinical trial, a type of research study, involving treatment with an investigational (experimental) drug called PCI-32765 (Ibrutinib), a "kinase inhibitor". "Kinases" are proteins that are inside of cells and help them to live and grow. The specific kinase inhibited or blocked by this study drug is believed to help blood cancer cells grow and live. By inhibiting or "blocking" the activity of this kinase, it is possible that the study drug may be able to kill the cancer cells or stop them from growing. This study will involve treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL) that has not responded to or has relapsed after standard treatment. This trial is studying how effective PCI-32765 is at treating CLL, SLL, or B-PLL and all the effects, good and/or bad, treatment with this drug has on patients and their cancers.
Interventions
DRUGibrutinib
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OTHERCorrelative laboratory samples
Blood samples will be collected and used for pharmacodynamic testing. Samples will be collected pre-dose on Cycle 1 Day 1 and 2 hours post-dose Cycle 1 Day 1, pre-dose on Day 2 and Day 8 of Cycle 1 and pre-dose on Day 1 of Cycles 2 and 3 and then every 3 cycles thereafter for 1 year (Cycle 15 Day 1). Samples will also be collected at the time of relapse and at any time when bone marrow biopsy is performed.
OTHERquality of life assessment
During screening, sociodemographic information (e.g., age, race, marital status) and reports of recent (last year) stressful events will be obtained. The assessment will consist of measures of emotional distress, depressive symptoms, and quality of life. Quality of life measures will be administered during screening and on Days 1 (±3), 8 (±3),, 15 (±3),, 22 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru month 24.
Sponsors
Kami Maddocks, MD
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
* Confirmed diagnosis of relapsed/refractory CLL/SLL who require treatment and have failed at least one prior therapy. * Patients must have available results of interphase cytogenetics CLL fluorescent in situ hybridization (FISH) panel; the cytogenetic analysis must be done prior to starting therapy but after any recent therapy * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Life expectancy greater than 2 months * Bilirubin =\< 1.5 X the institutional upper limit of normal unless due to Gilbert's disease or disease related to Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 X the institutional upper limit of normal unless disease related * Creatinine =\< 1.5 X the institutional upper limit of normal unless disease related * Absolute neutrophil count (ANC) \>= 0.75 X 10\^9/L * Platelet count \>= 30 X 10\^9/L * Agree to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children * Ability to understand and the willingness to sign a written informed consent document * Patients with uncontrolled or active infection requiring antibiotic therapy; patients with controlled infections who are receiving extended antibiotics or prophylactic therapy are not excluded
Exclusion criteria
* Patients who have had chemotherapy, radiotherapy or immunotherapy within 4 weeks prior to the first dose of study drug (corticosteroids for disease-related symptoms allowed but doses equivalent to \> 20 mg prednisone orally per day require 1 week washout before study drug administration or steroid dose must be equal to =\< 20 mg prednisone orally daily) * Patients who have not recovered from adverse events of \>= grade 3 toxicity due to agents administered more than 4 weeks ago * Receiving any other investigational agents * Previously randomized to any PCI-32765 clinical trial * Known secondary malignancy that limits survival to less than two years * Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction * Patients requiring anti-coagulation with warfarin or other Vitamin K antagonists or heparin products including low molecular weight heparin (LMWH) * Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification * Patients requiring treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) and/or cytochrome P450 2D6 (CYP2D6) inhibitor * Patients with 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 * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification * Active central nervous system (CNS) involvement by lymphoma * Pregnant or women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL. | up to 2 years | We will summarize our findings for this endpoint independently as well within each cohort (del17p vs other cytogenetic groups). We will evaluate the proportion of patients who are progression-free and alive at two years or have gone on to transplant (treatment successes) over the total number of evaluable patients; eligible patients who received at least one dose of therapy are considered evaluable. Assuming that the number of treatment successes as defined above is binomially distributed, we will also include 95% binomial confidence intervals for the estimates corresponding to each cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines | up to 2 years | Responders were subjects who achieved a complete response (CR), partial response (PR) or PR with persistent lymphocytosis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients | Up to 6 months | The 6 month overall response rates overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Percentage of Patients With Overall Survival (OS) | 2 years | Time from date of first treatment with ibrutinib until the date of death from any cause or the date of last contact for those alive. |
| 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765 | 2 years | Time from date of first treatment with ibrutinib until the date of progression or death from any cause. Those alive and progression free are censored at the date of last clinical assessment. |
| Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Up to 2 years post treatment | Adverse events grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with the attribution of either definite, possible or probable related. |
| Resistance Studies of Ibrutinib | Up to 4 years | Percentage of patients with BTK C481S mutation or PLCG2 mutation |
| Decrease in Immune Suppression of CLL Cells | up to 3 months | — |
| Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention | Up to 2 years | The number of participants with successful Allogenic Stem Cell Transplant |
| Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R) | Up to 2 years | Cancer-Specific Stress was measured by the Impact of Event Scale-Revised Participants rated the intensity of these feelings using a five-point Likert scale ranging from 0=not at all to 4=extremely. Patients rated the frequency of their feelings or events for the previous week before treatment. The items were summed for a total score that ranged from 0 to 64 |
| Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II) | at 5 months | The Beck Depression Inventory-2nd edition is a 21-item measure of depressive symptoms. Scores were calculated representing the cognitive-affective and the somatic symptoms associated with depression (e.g. sadness, pessimism, loss of pleasure) during past month on scale from 0 to 3. Items were summed, with higher scores indicating more depressive symptoms. The scores on the scale from range from 0 to 42. |
| Negative Mood Quality of Life Measured by a 37-item Questionnaire | at 5 months | The Profile of Mood States-Short Form (POMS-SF) yields six subscales, Tension, Depression, Anger, Vigor, Fatigue, and Confusion. A total mood disturbance score is found by summing the six subscales. Total Mood Disturbance (TMD) scores range from -24 to 124 with higher scores indicating greater mood disturbance. |
| Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study | at 5 months | SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning. |
| Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory | at 5 months | The Fatigue Interference quality of life measures is a 11-item self reported questionnaire used to measure frequency, severity and daily pattern of fatigue Symptoms as well as impact of QOL in the past week. The Total Disruption Index (TDI) an 7 item subset of FSI was used. Items were rated on a 11-point Likert scale from 0=no interference to 10=extreme interference. Total scores could range from 0 to 70, with higher scores indicating greater fatigue interference. |
| Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale | at 5 months | Sleep problems quality of life measures is a six-item sleep problems index I of the Medical Outcomes Study-Sleep Scale used to assess sleep problems. Participants reported how often they experience six specific difficulties with sleep on a 6-point Likert scale (1=All of the time to 6=None of the time). Scores transformed into a 0-100 scale with higher scores indicating greater sleep problems. |
| Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey | up to 5 months | Physical Health Quality of life measures were administered during screening and on Days 1 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru Cycle 24 and at time of progression and /or end of treatment. SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKami Maddocks, MD
Ohio State University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ibrutinib) Patients were treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy. Patients received ibrutinib orally (PO) once daily(QD)on days 1-28. Courses repeat every 28 days in the absence of disease progression | 152 |
| Total | 152 |
Baseline characteristics
| Characteristic | Treatment (Ibrutinib) |
|---|---|
| Age, Continuous Del17p patients | 66 years |
| Age, Continuous Non-Del17p patients | 64 years |
| Region of Enrollment United States | 152 patients |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| other Total, other adverse events | 152 / 152 |
| serious Total, serious adverse events | 152 / 152 |
Outcome results
Primary
Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.
We will summarize our findings for this endpoint independently as well within each cohort (del17p vs other cytogenetic groups). We will evaluate the proportion of patients who are progression-free and alive at two years or have gone on to transplant (treatment successes) over the total number of evaluable patients; eligible patients who received at least one dose of therapy are considered evaluable. Assuming that the number of treatment successes as defined above is binomially distributed, we will also include 95% binomial confidence intervals for the estimates corresponding to each cohort.
Time frame: up to 2 years
Population: There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL. | All patients | 64 percentage of patients |
| Treatment (Ibrutinib) | Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL. | Del(17p) | 64 percentage of patients |
| Treatment (Ibrutinib) | Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL. | non-Del(17p) | 64 percentage of patients |
Secondary
2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765
Time from date of first treatment with ibrutinib until the date of progression or death from any cause. Those alive and progression free are censored at the date of last clinical assessment.
Time frame: 2 years
Population: There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765 | All patients | 69 percent of patients |
| Treatment (Ibrutinib) | 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765 | Del(17p) | 66 percent of patients |
| Treatment (Ibrutinib) | 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765 | non-Del(17p) | 72 percent of patients |
Secondary
Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines
Responders were subjects who achieved a complete response (CR), partial response (PR) or PR with persistent lymphocytosis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: up to 2 years
Population: There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines | All patients | 63 percentage of patients |
| Treatment (Ibrutinib) | Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines | Del(17p) | 66 percentage of patients |
| Treatment (Ibrutinib) | Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines | non-Del(17p) | 59 percentage of patients |
Secondary
Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R)
Cancer-Specific Stress was measured by the Impact of Event Scale-Revised Participants rated the intensity of these feelings using a five-point Likert scale ranging from 0=not at all to 4=extremely. Patients rated the frequency of their feelings or events for the previous week before treatment. The items were summed for a total score that ranged from 0 to 64
Time frame: Up to 2 years
Population: Data was reported for start of treatment only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R) | 9.18 units on a scale | Standard Deviation 8.35 |
Secondary
Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II)
The Beck Depression Inventory-2nd edition is a 21-item measure of depressive symptoms. Scores were calculated representing the cognitive-affective and the somatic symptoms associated with depression (e.g. sadness, pessimism, loss of pleasure) during past month on scale from 0 to 3. Items were summed, with higher scores indicating more depressive symptoms. The scores on the scale from range from 0 to 42.
Time frame: at 5 months
Population: Data was reported for month 5 from start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II) | 1.88 units on a scale | Standard Deviation 3.11 |
Secondary
Decrease in Immune Suppression of CLL Cells
Time frame: up to 3 months
Population: Data was not collect and analyzed for this outcome measure
Secondary
Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention
The number of participants with successful Allogenic Stem Cell Transplant
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ibrutinib) | Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention | 1 participants |
Secondary
Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory
The Fatigue Interference quality of life measures is a 11-item self reported questionnaire used to measure frequency, severity and daily pattern of fatigue Symptoms as well as impact of QOL in the past week. The Total Disruption Index (TDI) an 7 item subset of FSI was used. Items were rated on a 11-point Likert scale from 0=no interference to 10=extreme interference. Total scores could range from 0 to 70, with higher scores indicating greater fatigue interference.
Time frame: at 5 months
Population: Data was reported for month 5 from the start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory | 9.70 units on a scale | Standard Deviation 13.11 |
Secondary
Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study
SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning.
Time frame: at 5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study | 53.98 units on a scale | Standard Deviation 8.72 |
Secondary
Negative Mood Quality of Life Measured by a 37-item Questionnaire
The Profile of Mood States-Short Form (POMS-SF) yields six subscales, Tension, Depression, Anger, Vigor, Fatigue, and Confusion. A total mood disturbance score is found by summing the six subscales. Total Mood Disturbance (TMD) scores range from -24 to 124 with higher scores indicating greater mood disturbance.
Time frame: at 5 months
Population: Data was reported for month 5 from start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Negative Mood Quality of Life Measured by a 37-item Questionnaire | 0.89 units on a scale | Standard Deviation 18.12 |
Secondary
Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients
The 6 month overall response rates overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 6 months
Population: There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients | All patients | 63 patients |
| Treatment (Ibrutinib) | Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients | Del(17p) | 66 patients |
| Treatment (Ibrutinib) | Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients | Non-del(17p) | 59 patients |
Secondary
Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Adverse events grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with the attribution of either definite, possible or probable related.
Time frame: Up to 2 years post treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Anemia | 13 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Febrible Neutropenia | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Leukocytosis | 18 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Atrial Fibrillation | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Diarrhea | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Gastric Hemorrhage | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Gastrointestinal Disorders-other | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Mucositis Oral | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Nausea | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Death | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Edema Limb | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Fatigue | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | General Disorders and Admin Site Conditions | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Cholecystitis | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Bronchial Infection | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Infections and Infestations-other | 4 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Lung Infection | 10 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Otitis Media | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Sepsis | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Skin Infection | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Urinary Tract Infection | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Alanine Aminotransferase Increased | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Blood Bilirubin Increased | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Lymphocyte Count Decreased | 14 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Lymphocyte Count Increased | 54 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Neutrophil Count Decreased | 40 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Platelet Count Decreased | 8 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | White Blood Cell Decreased | 10 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hyperuricemia | 4 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hypophosphatemia | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Arthralgia | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Arthritis | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hematuria | 2 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hypoxia | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Respiratory Failure | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Rash Maculo-papular | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hematoma | 1 patients |
| Treatment (Ibrutinib) | Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Hypertension | 7 patients |
Secondary
Percentage of Patients With Overall Survival (OS)
Time from date of first treatment with ibrutinib until the date of death from any cause or the date of last contact for those alive.
Time frame: 2 years
Population: There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ibrutinib) | Percentage of Patients With Overall Survival (OS) | All patients | 78 percent of patients |
| Treatment (Ibrutinib) | Percentage of Patients With Overall Survival (OS) | Del(17p) | 75 percent of patients |
| Treatment (Ibrutinib) | Percentage of Patients With Overall Survival (OS) | non-Del(17p) | 81 percent of patients |
Secondary
Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey
Physical Health Quality of life measures were administered during screening and on Days 1 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru Cycle 24 and at time of progression and /or end of treatment. SF-12 assesses aspects of quality of life including physical functioning, role functioning-physical, bodily pain, general health perceptions, vitality, social functioning, role functioning-emotional, and mental health. Subscale raw scores are transformed to put each subscale on a 0-100 range with higher scores indicative of greater functioning. Subscale scores are standardized based on US General Population norms and aggregated based on factor score coefficients into two component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Component scores are norm-based t-scores meaning scores above 50 indicate better functioning than average functioning while scores below 50 indicate worse functioning.
Time frame: up to 5 months
Population: Data was reported for month 5 from start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey | 44.23 units on a scale | Standard Deviation 11.31 |
Secondary
Resistance Studies of Ibrutinib
Percentage of patients with BTK C481S mutation or PLCG2 mutation
Time frame: Up to 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ibrutinib) | Resistance Studies of Ibrutinib | 13.2 percentage of patients |
Secondary
Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale
Sleep problems quality of life measures is a six-item sleep problems index I of the Medical Outcomes Study-Sleep Scale used to assess sleep problems. Participants reported how often they experience six specific difficulties with sleep on a 6-point Likert scale (1=All of the time to 6=None of the time). Scores transformed into a 0-100 scale with higher scores indicating greater sleep problems.
Time frame: at 5 months
Population: Data was reported for month 5 from start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Ibrutinib) | Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale | 24.08 units on a scale | Standard Deviation 17.23 |