PCI-32765 (Ibrutinib) in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia

• Sponsor: Kami Maddocks, MD (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01589302
• Collaborator: (none)
• Enrollment: 154
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 127.3
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory/Relapsed Chronic Lymphocytic Leukemia	Drug: ibrutinib; Other: Correlative laboratory samples; Other: quality of life assessment	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765(Ibrutinib), in Relapsed and Refractory Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and B-cell Prolymphocytic Leukemia (B-PLL)
• Actual Study Start Date: May 21, 2012
• Actual Primary Completion Date: Jul 28, 2016
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (ibrutinib) Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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.

Drug: ibrutinib; 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.; Other Names: Bruton's tyrosine kinase inhibitor PCI-32765 BTK inhibitor PCI-32765 PCI-32765 ; Other: Correlative 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.; Other Names: laboratory biomarker anyalysis ; Other: quality 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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

3. 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.

4. 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.

5. 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.

6. Resistance Studies of Ibrutinib [Up to 4 years]

   Percentage of patients with BTK C481S mutation or PLCG2 mutation

7. Decrease in Immune Suppression of CLL Cells [up to 3 months]

8. 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

9. 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

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University Medical Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Kami Maddocks, MD

Investigators

• Principal Investigator: Kami Maddocks, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Jamesline

Publications

None provided.

• Responsible Party: Kami Maddocks, MD, Principal Investigator, Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01589302
• Other Study ID Numbers: OSU-11133; NCI-2012-00560
• First Posted: May 1, 2012
• Last Update Posted: Jul 14, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kami Maddocks, MD, Principal Investigator, Ohio State University Comprehensive Cancer Center: Bruton's Tyrosine Kinase; CLL; SLL; B-PLL
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, B-Cell

Study Results

Participant Flow

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	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
Period Title: Overall Study
STARTED	154
Del17p Patients	76
Non-Del17p Patients	76
COMPLETED	152
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	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
Overall Participants	152
Age (years) [Median (Full Range) ]
Del17p patients	66
Non-Del17p patients	64
Sex: Female, Male (Count of Participants)
Female	44 28.9%
Male	108 71.1%
Region of Enrollment (patients) [Number]
United States	152

Outcome Measures

1. Primary Outcome

Title	Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.
Description	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

Outcome Measure Data

Analysis Population Description

There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
All patients	64
Del(17p)	64
non-Del(17p)	64

2. Secondary Outcome

Title	Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines
Description	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

Outcome Measure Data

Analysis Population Description

There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
All patients	63
Del(17p)	66
non-Del(17p)	59

3. Secondary Outcome

Title	Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients
Description	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

Outcome Measure Data

Analysis Population Description

There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease pro
Measure Participants	152
All patients	63
Del(17p)	66
Non-del(17p)	59

4. Secondary Outcome

Title	Percentage of Patients With Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description

There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
All patients	78
Del(17p)	75
non-Del(17p)	81

5. Secondary Outcome

Title	2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765
Description	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

Outcome Measure Data

Analysis Population Description

There are 2 different cohorts Del (17p) and Non-Del (17p) each with 76 patients

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
All patients	69
Del(17p)	66
non-Del(17p)	72

6. Secondary Outcome

Title	Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
Anemia	13
Febrible Neutropenia	2
Leukocytosis	18
Atrial Fibrillation	1
Diarrhea	2
Gastric Hemorrhage	1
Gastrointestinal Disorders-other	1
Mucositis Oral	1
Nausea	2
Death	1
Edema Limb	1
Fatigue	1
General Disorders and Admin Site Conditions	2
Cholecystitis	1
Bronchial Infection	1
Infections and Infestations-other	4
Lung Infection	10
Otitis Media	1
Sepsis	2
Skin Infection	2
Urinary Tract Infection	1
Alanine Aminotransferase Increased	1
Blood Bilirubin Increased	1
Lymphocyte Count Decreased	14
Lymphocyte Count Increased	54
Neutrophil Count Decreased	40
Platelet Count Decreased	8
White Blood Cell Decreased	10
Hyperuricemia	4
Hypophosphatemia	1
Arthralgia	2
Arthritis	1
Hematuria	2
Hypoxia	1
Respiratory Failure	1
Rash Maculo-papular	1
Hematoma	1
Hypertension	7

7. Secondary Outcome

Title	Resistance Studies of Ibrutinib
Description	Percentage of patients with BTK C481S mutation or PLCG2 mutation
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease pro
Measure Participants	152
Number (95% Confidence Interval) [percentage of patients]	13.2

8. Secondary Outcome

Title	Decrease in Immune Suppression of CLL Cells
Time Frame	up to 3 months

Outcome Measure Data

Analysis Population Description

Data was not collect and analyzed for this outcome measure

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease pro
Measure Participants	0

9. Secondary Outcome

Title	Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention
Description	The number of participants with successful Allogenic Stem Cell Transplant
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
Number [participants]	1 0.7%

10. Secondary Outcome

Title	Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R)
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for start of treatment only

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	152
Mean (Standard Deviation) [units on a scale]	9.18 (8.35)

11. Secondary Outcome

Title	Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II)
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for month 5 from start of treatment

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	130
Mean (Standard Deviation) [units on a scale]	1.88 (3.11)

12. Secondary Outcome

Title	Negative Mood Quality of Life Measured by a 37-item Questionnaire
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for month 5 from start of treatment

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	128
Mean (Standard Deviation) [units on a scale]	0.89 (18.12)

13. Secondary Outcome

Title	Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	126
Mean (Standard Deviation) [units on a scale]	53.98 (8.72)

14. Secondary Outcome

Title	Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for month 5 from the start of treatment

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	129
Mean (Standard Deviation) [units on a scale]	9.70 (13.11)

15. Secondary Outcome

Title	Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for month 5 from start of treatment

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	129
Mean (Standard Deviation) [units on a scale]	24.08 (17.23)

16. Secondary Outcome

Title	Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey
Description	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

Outcome Measure Data

Analysis Population Description

Data was reported for month 5 from start of treatment

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression
Measure Participants	126
Mean (Standard Deviation) [units on a scale]	44.23 (11.31)

Adverse Events

Arm/Group Title	Treatment (Ibrutinib)
Arm/Group Description	Patients treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) 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. ibrutinib: Patients received ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progres
All Cause Mortality
	Treatment (Ibrutinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Ibrutinib)
	Affected / at Risk (%)	# Events
Total	152/152 (100%)
Blood and lymphatic system disorders
Febrile Neutropenia	5/152 (3.3%)	5
Hemolytic Uremic Syndrome	1/152 (0.7%)	1
Lymph Node Pain	1/152 (0.7%)	1
Cardiac disorders
Atrial Fibrillation	1/152 (0.7%)	1
Cardiac Arrest	1/152 (0.7%)	1
Cardiac Disorders-other	1/152 (0.7%)	4
Myocardial Infarction	1/152 (0.7%)	1
Ventricular Arrythmia	1/152 (0.7%)	1
Eye disorders
Blurred Vision	1/152 (0.7%)	1
Gastrointestinal disorders
Colonic Perforation	1/152 (0.7%)	1
Diarrhea	3/152 (2%)	3
Enterocolitis	1/152 (0.7%)	1
Esophageal Ulcer	1/152 (0.7%)	1
Gastric Hemorrhage	1/152 (0.7%)	1
Gastrointestinal Disorders-other	3/152 (2%)	4
Jejunal Hemorrhage	1/152 (0.7%)	1
Small Intestinal Obstruction	2/152 (1.3%)	2
Chills	1/152 (0.7%)	1
General disorders
Death NOS	5/152 (3.3%)	5
Edema Limbs	1/152 (0.7%)	1
Fatigue	1/152 (0.7%)	1
Fever	4/152 (2.6%)	4
General Disorders and Administration Site Conditions - Other	3/152 (2%)	3
Non-Cardiac Chest Pain	1/152 (0.7%)	1
Sudden Death NOS	1/152 (0.7%)	1
Hepatobiliary disorders
Cholecystitis	2/152 (1.3%)	4
Immune system disorders
Immune System Disorders - Other	1/152 (0.7%)	1
Infections and infestations
Bone Infection	3/152 (2%)	3
Bronchial Infection	4/152 (2.6%)	4
Catheter Related Infection	2/152 (1.3%)	2
Enterocolitis Infectious	3/152 (2%)	3
Infections and Infestations-other	13/152 (8.6%)	16
Lung Infection	32/152 (21.1%)	53
Otitis Media	2/152 (1.3%)	2
Pharyngitis	1/152 (0.7%)	1
Sepsis	6/152 (3.9%)	7
Sinusitis	1/152 (0.7%)	1
Skin Infection	4/152 (2.6%)	4
Soft Tissue Infection	2/152 (1.3%)	3
Upper Respiratory Infection	5/152 (3.3%)	5
Urinary Tract Infection	3/152 (2%)	8
Injury, poisoning and procedural complications
Fall	1/152 (0.7%)	1
Fracture	1/152 (0.7%)	1
Injury, Poisoning and Procedural Complications - Other	3/152 (2%)	3
Intestinal Stoma Obstruction	1/152 (0.7%)	1
Postoperative Hemorrhage	1/152 (0.7%)	1
Spinal Fracture	1/152 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	3/152 (2%)	3
Hypercalcemia	2/152 (1.3%)	2
Hyperglycemia	1/152 (0.7%)	1
Hyperkalemia	1/152 (0.7%)	1
Hyponatremia	1/152 (0.7%)	1
Metabolism and Nutrition Disorders - Other	4/152 (2.6%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	2/152 (1.3%)	3
Back Pain	3/152 (2%)	3
Generalized Muscle Weakness	1/152 (0.7%)	1
Muscle Weakness Left Sided	1/152 (0.7%)	1
Musculoskeletal and Connective Tissue Disorder - Other	3/152 (2%)	3
Nervous system disorders
Intracranial Hemorrhage	2/152 (1.3%)	2
Leukoencephalopathy	2/152 (1.3%)	2
Memory Impairement	1/152 (0.7%)	1
Nervous System Disorders - Other	3/152 (2%)	4
Syncope	2/152 (1.3%)	2
Transient Ischemic Attacks	2/152 (1.3%)	2
Tremor	1/152 (0.7%)	1
Psychiatric disorders
Psychiatric Disorders-Other	1/152 (0.7%)	1
Renal and urinary disorders
Renal and Urinary Disorders - Other	1/152 (0.7%)	1
Urinary Tract Obstruction	1/152 (0.7%)	1
Reproductive system and breast disorders
Reproductive System and Breast Disorders - Other	1/152 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/152 (0.7%)	1
Respiratory, Thoracic, and Mediastinal Disorders - Other	1/152 (0.7%)	1
Skin and subcutaneous tissue disorders
Rash Maculo-papular	1/152 (0.7%)	1
Surgical and medical procedures
Surgical and Medical Procedures - Other	4/152 (2.6%)	4
Vascular disorders
Hematoma	1/152 (0.7%)	2
Hypotension	1/152 (0.7%)	1
Superior Vena Cava Syndrom	1/152 (0.7%)	1
Thromboembolic Events	2/152 (1.3%)	2
Vascular Disorders- Other	1/152 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Ibrutinib)
	Affected / at Risk (%)	# Events
Total	152/152 (100%)
Blood and lymphatic system disorders
Anemia	43/152 (28.3%)	51
Leukocytosis	25/152 (16.4%)	29
Lymph node pain	14/152 (9.2%)	16
Cardiac disorders
Atrial Fibrillation	13/152 (8.6%)	15
Palpitations	12/152 (7.9%)	15
Sinus Bradycardia	24/152 (15.8%)	28
Sinus Tachycardia	9/152 (5.9%)	11
Ear and labyrinth disorders
Ear and Labyrinth disorders	10/152 (6.6%)	12
Hearing impaired	8/152 (5.3%)	8
Vertigo	8/152 (5.3%)	8
Eye disorders
Blurred vision	19/152 (12.5%)	21
Cataract	13/152 (8.6%)	13
Conjunctivitis	8/152 (5.3%)	9
Dry eye	12/152 (7.9%)	13
Eye Disorders	35/152 (23%)	41
Watering eyes	8/152 (5.3%)	8
Gastrointestinal disorders
Abdominal Pain	34/152 (22.4%)	39
Bloating	24/152 (15.8%)	24
Constipation	51/152 (33.6%)	66
Diarrhea	100/152 (65.8%)	190
Dry mouth	15/152 (9.9%)	15
Dyspepsia	15/152 (9.9%)	17
Dysphagia	10/152 (6.6%)	10
Flatulence	17/152 (11.2%)	18
Gastrointestional Disorder	73/152 (48%)	103
Mucositis	70/152 (46.1%)	127
Nausea	56/152 (36.8%)	86
Oral Hemorrhage	28/152 (18.4%)	37
Oral Pain	7/152 (4.6%)	8
Stomach Pain	10/152 (6.6%)	10
Vomiting	41/152 (27%)	59
General disorders
Chills	36/152 (23.7%)	42
Edema Limbs	49/152 (32.2%)	59
Fatigue	83/152 (54.6%)	99
Fever	41/152 (27%)	55
Flu Like Symptoms	13/152 (8.6%)	15
General Disorders	27/152 (17.8%)	34
Non-Cardiac chest pain	12/152 (7.9%)	12
Pain	33/152 (21.7%)	42
Infections and infestations
Bronchial Infection	18/152 (11.8%)	21
Eye Infection	8/152 (5.3%)	9
Infections and Infestations	32/152 (21.1%)	41
Lung Infection	30/152 (19.7%)	43
Nail Infection	9/152 (5.9%)	9
Paronychia	11/152 (7.2%)	18
Sinusitis	49/152 (32.2%)	68
Skin Infection	35/152 (23%)	43
Upper Respiratory Infection	72/152 (47.4%)	129
Urinary Tract Infection	30/152 (19.7%)	52
Injury, poisoning and procedural complications
Bruising	70/152 (46.1%)	93
Fall	20/152 (13.2%)	32
Injury, Poisoning and procedural complications	7/152 (4.6%)	7
Investigations
Lymphocyte count decreased	25/152 (16.4%)	36
Lymphocyte count increased	70/152 (46.1%)	87
Neutrophil count decreased	80/152 (52.6%)	166
Platelet count decreased	44/152 (28.9%)	52
Weight gain	65/152 (42.8%)	75
Weight loss	39/152 (25.7%)	53
White Blood cell decreased	27/152 (17.8%)	38
Metabolism and nutrition disorders
Anorexia	39/152 (25.7%)	39
Hyperglycemia	17/152 (11.2%)	30
Hyperkalemia	8/152 (5.3%)	9
Hyperuricemia	17/152 (11.2%)	25
Hypokalemia	9/152 (5.9%)	14
Hyponatremia	14/152 (9.2%)	15
Hypophosphatemia	12/152 (7.9%)	15
Musculoskeletal and connective tissue disorders
Arthralgia	56/152 (36.8%)	77
Arthritis	24/152 (15.8%)	26
Back pain	37/152 (24.3%)	41
Bone pain	12/152 (7.9%)	12
Musculoskeletal and Connective tissue disorder-other	104/152 (68.4%)	123
Myalgia	29/152 (19.1%)	34
Neck pain	9/152 (5.9%)	10
Pain Extremity	29/152 (19.1%)	34
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified-other	37/152 (24.3%)	49
Nervous system disorders
Dizziness	55/152 (36.2%)	69
Dysgeusia	17/152 (11.2%)	18
Headache	63/152 (41.4%)	79
Nervous System Disorders-other	10/152 (6.6%)	10
Paresthesia	48/152 (31.6%)	54

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.