A Phase 2 interventional study of ibrutinib and Correlative laboratory samples in Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma and Refractory/Relapsed Chronic Lymphocytic Leukemia, sponsored by Kami Maddocks, MD. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-13.
Sponsored by Kami Maddocks, MD · Phase 2, Interventional, and Treatment
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.
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.
88 studies on the registry are indexed under Leukemia, Prolymphocytic; 7 are open to participants now.
This study's enrollment of 154 is above the median of 30 across 79 interventional studies indexed under Leukemia, Prolymphocytic.
Browse Leukemia, Prolymphocytic studies →Kami Maddocks, MD is the lead sponsor of 3 studies on the registry; none are open to participants now.
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Exclusion Criteria:
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 · Other: Correlative laboratory samples · Other: quality of life assessment
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.
Also known as: Bruton's tyrosine kinase inhibitor PCI-32765, BTK inhibitor PCI-32765, PCI-32765
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.
Also known as: laboratory biomarker anyalysis
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.
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
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
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
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
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
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
Resistance Studies of Ibrutinib
Percentage of patients with BTK C481S mutation or PLCG2 mutation
Time frame: Up to 4 years
Decrease in Immune Suppression of CLL Cells
Time frame: up to 3 months
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
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
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
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
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
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
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
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
| Milestone | Treatment (Ibrutinib) |
|---|---|
| Started | 154 |
| Del17p patients | 76 |
| Non-del17p patients | 76 |
| Completed | 152 |
| Not completed | 2 |
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.
| percentage of patients | Treatment (Ibrutinib) |
|---|---|
| All patients | 64 (57 to 72) |
| Del(17p) | 64 (54 to 75) |
| non-Del(17p) | 64 (54 to 75) |
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.
| percentage of patients | Treatment (Ibrutinib) |
|---|---|
| All patients | 63 (55 to 70) |
| Del(17p) | 66 (55 to 76) |
| non-Del(17p) | 59 (48 to 70) |
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
| patients | Treatment (Ibrutinib) |
|---|---|
| All patients | 63 (55 to 70) |
| Del(17p) | 66 (55 to 76) |
| Non-del(17p) | 59 (48 to 70) |
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.
| percent of patients | Treatment (Ibrutinib) |
|---|---|
| All patients | 78 (71 to 84) |
| Del(17p) | 75 (63 to 83) |
| non-Del(17p) | 81 (71 to 89) |
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.
| percent of patients | Treatment (Ibrutinib) |
|---|---|
| All patients | 69 (61 to 76) |
| Del(17p) | 66 (54 to 76) |
| non-Del(17p) | 72 (60 to 81) |
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.
| patients | Treatment (Ibrutinib) |
|---|---|
| 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 |
Percentage of patients with BTK C481S mutation or PLCG2 mutation
| percentage of patients | Treatment (Ibrutinib) |
|---|---|
| Resistance Studies of Ibrutinib | 13.2 (8.2 to 19.6) |
No measurements were reported for this outcome.
The number of participants with successful Allogenic Stem Cell Transplant
| participants | Treatment (Ibrutinib) |
|---|---|
| Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention | 1 |
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
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R) | 9.18 ± 8.35 |
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.
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II) | 1.88 ± 3.11 |
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.
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Negative Mood Quality of Life Measured by a 37-item Questionnaire | 0.89 ± 18.12 |
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.
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study | 53.98 ± 8.72 |
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.
| units on a scale | 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 ± 13.11 |
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.
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale | 24.08 ± 17.23 |
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.
| units on a scale | Treatment (Ibrutinib) |
|---|---|
| Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey | 44.23 ± 11.31 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Ibrutinib) | — | 152/152 (100%) | 152/152 (100%) |
| Event | Treatment (Ibrutinib) |
|---|---|
| Lung InfectionInfections and infestations | 32/152 |
| Infections and Infestations-otherInfections and infestations | 13/152 |
| SepsisInfections and infestations | 6/152 |
| Febrile NeutropeniaBlood and lymphatic system disorders | 5/152 |
| Death NOSGeneral disorders and administration site conditions | 5/152 |
| Upper Respiratory InfectionInfections and infestations | 5/152 |
| FeverGeneral disorders and administration site conditions | 4/152 |
| Bronchial InfectionInfections and infestations | 4/152 |
| Skin InfectionInfections and infestations | 4/152 |
| Metabolism and Nutrition Disorders - OtherMetabolism and nutrition disorders | 4/152 |
| Event | Treatment (Ibrutinib) |
|---|---|
| Musculoskeletal and Connective tissue disorder-otherMusculoskeletal and connective tissue disorders | 104/152 |
| DiarrheaGastrointestinal disorders | 100/152 |
| FatigueGeneral disorders | 83/152 |
| Neutrophil count decreasedInvestigations | 80/152 |
| Gastrointestional DisorderGastrointestinal disorders | 73/152 |
| Upper Respiratory InfectionInfections and infestations | 72/152 |
| MucositisGastrointestinal disorders | 70/152 |
| BruisingInjury, poisoning and procedural complications | 70/152 |
| Lymphocyte count increasedInvestigations | 70/152 |
| Weight gainInvestigations | 65/152 |
| Age, Continuous(years) | Treatment (Ibrutinib) |
|---|---|
| Del17p patients | 66 (42 to 91) |
| Non-Del17p patients | 64 (26 to 85) |
| Sex: Female, Male(Participants) | Treatment (Ibrutinib) |
|---|---|
| Female | 44 |
| Male | 108 |
| Region of Enrollment(patients) | Treatment (Ibrutinib) |
|---|---|
| United States | 152 |
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