NCT01589302

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

Active, enrolled Phase 2 Results posted Last updated 13 April 2026

What this trial tests

Phase 2 trial testing ibrutinib in Prolymphocytic Leukemia in 154 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

21 May 2012

Primary endpoint
28 July 2016

31 October 2026

Quick facts

Lead sponsor	Kami Maddocks, MD
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	154
Start date	21 May 2012
Primary completion	28 July 2016
Estimated completion	31 October 2026
Sites	1 location across United States

Drugs / interventions tested

• ibrutinib (ibrutinib) — full drug profile →
• Correlative laboratory samples
• quality of life assessment

Conditions studied

• Prolymphocytic Leukemia — all drugs for Prolymphocytic Leukemia →
• Recurrent Small Lymphocytic Lymphoma — all drugs for Recurrent Small Lymphocytic Lymphoma →
• Refractory/Relapsed Chronic Lymphocytic Leukemia — all drugs for Refractory/Relapsed Chronic Lymphocytic Leukemia →

Sponsor

Kami Maddocks, MD — full company profile →

Who can join

18 and older, any sex, with Prolymphocytic Leukemia or Recurrent Small Lymphocytic Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

All patients

Group	Value	95% CI
Treatment (Ibrutinib)	64	57 – 72

Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	64	54 – 75

non-Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	64	54 – 75

Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines Secondary · 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.

All patients

Group	Value	95% CI
Treatment (Ibrutinib)	63	55 – 70

Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	66	55 – 76

non-Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	59	48 – 70

Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients Secondary · 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

All patients

Group	Value	95% CI
Treatment (Ibrutinib)	63	55 – 70

Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	66	55 – 76

Non-del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	59	48 – 70

Percentage of Patients With Overall Survival (OS) Secondary · 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.

All patients

Group	Value	95% CI
Treatment (Ibrutinib)	78	71 – 84

Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	75	63 – 83

non-Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	81	71 – 89

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

All patients

Group	Value	95% CI
Treatment (Ibrutinib)	69	61 – 76

Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	66	54 – 76

non-Del(17p)

Group	Value	95% CI
Treatment (Ibrutinib)	72	60 – 81

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

Anemia

Group	Value	95% CI
Treatment (Ibrutinib)	13

Febrible Neutropenia

Group	Value	95% CI
Treatment (Ibrutinib)	2

Leukocytosis

Group	Value	95% CI
Treatment (Ibrutinib)	18

Atrial Fibrillation

Group	Value	95% CI
Treatment (Ibrutinib)	1

Diarrhea

Group	Value	95% CI
Treatment (Ibrutinib)	2

Gastric Hemorrhage

Group	Value	95% CI
Treatment (Ibrutinib)	1

Gastrointestinal Disorders-other

Group	Value	95% CI
Treatment (Ibrutinib)	1

Mucositis Oral

Group	Value	95% CI
Treatment (Ibrutinib)	1

Resistance Studies of Ibrutinib Secondary · Up to 4 years

Percentage of patients with BTK C481S mutation or PLCG2 mutation

Group	Value	95% CI
Treatment (Ibrutinib)	13.2	8.2 – 19.6

Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention Secondary · Up to 2 years

The number of participants with successful Allogenic Stem Cell Transplant

Group	Value	95% CI
Treatment (Ibrutinib)	1

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

Group	Value	95% CI
Treatment (Ibrutinib)	9.18	± 8.35

Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II) Secondary · 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.

Group	Value	95% CI
Treatment (Ibrutinib)	1.88	± 3.11

Negative Mood Quality of Life Measured by a 37-item Questionnaire Secondary · 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.

Group	Value	95% CI
Treatment (Ibrutinib)	0.89	± 18.12

Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study Secondary · 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-bas

Group	Value	95% CI
Treatment (Ibrutinib)	53.98	± 8.72

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Ibrutinib)

Serious: 152/152 (100%)

Deaths: —

Serious adverse events (78 terms)

Reaction	System	Treatment (Ibrutinib)
Lung Infection	Infections and infestations	—
Infections and Infestations-other	Infections and infestations	—
Sepsis	Infections and infestations	—
Febrile Neutropenia	Blood and lymphatic system disorders	—
Death NOS	General disorders and administration site conditions	—
Upper Respiratory Infection	Infections and infestations	—
Fever	General disorders and administration site conditions	—
Bronchial Infection	Infections and infestations	—
Skin Infection	Infections and infestations	—
Metabolism and Nutrition Disorders - Other	Metabolism and nutrition disorders	—
Surgical and Medical Procedures - Other	Surgical and medical procedures	—
Diarrhea	Gastrointestinal disorders	—
Gastrointestinal Disorders-other	Gastrointestinal disorders	—
General Disorders and Administration Site Conditions - Other	General disorders and administration site conditions	—
Bone Infection	Infections and infestations	—
Enterocolitis Infectious	Infections and infestations	—
Urinary Tract Infection	Infections and infestations	—
Injury, Poisoning and Procedural Complications - Other	Injury, poisoning and procedural complications	—
Dehydration	Metabolism and nutrition disorders	—
Back Pain	Musculoskeletal and connective tissue disorders	—
Musculoskeletal and Connective Tissue Disorder - Other	Musculoskeletal and connective tissue disorders	—
Nervous System Disorders - Other	Nervous system disorders	—
Small Intestinal Obstruction	Gastrointestinal disorders	—
Cholecystitis	Hepatobiliary disorders	—
Catheter Related Infection	Infections and infestations	—

Other adverse events (80 terms — click to expand)

Reaction	System	Treatment (Ibrutinib)
Musculoskeletal and Connective tissue disorder-other	Musculoskeletal and connective tissue disorders	—
Diarrhea	Gastrointestinal disorders	—
Fatigue	General disorders	—
Neutrophil count decreased	Investigations	—
Gastrointestional Disorder	Gastrointestinal disorders	—
Upper Respiratory Infection	Infections and infestations	—
Mucositis	Gastrointestinal disorders	—
Bruising	Injury, poisoning and procedural complications	—
Lymphocyte count increased	Investigations	—
Weight gain	Investigations	—
Headache	Nervous system disorders	—
Nausea	Gastrointestinal disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Dizziness	Nervous system disorders	—
Constipation	Gastrointestinal disorders	—
Edema Limbs	General disorders	—
Sinusitis	Infections and infestations	—
Paresthesia	Nervous system disorders	—
Platelet count decreased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Vomiting	Gastrointestinal disorders	—
Fever	General disorders	—
Weight loss	Investigations	—
Anorexia	Metabolism and nutrition disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Neoplasms benign, malignant and unspecified-other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Chills	General disorders	—
Eye Disorders	Eye disorders	—
Skin Infection	Infections and infestations	—
Abdominal Pain	Gastrointestinal disorders	—
Pain	General disorders	—
Infections and Infestations	Infections and infestations	—
Lung Infection	Infections and infestations	—
Urinary Tract Infection	Infections and infestations	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Pain Extremity	Musculoskeletal and connective tissue disorders	—
Oral Hemorrhage	Gastrointestinal disorders	—
General Disorders	General disorders	—
White Blood cell decreased	Investigations	—
Leukocytosis	Blood and lymphatic system disorders	—

Most-reported serious reactions: Lung Infection, Infections and Infestations-other, Sepsis, Febrile Neutropenia, Death NOS, Upper Respiratory Infection, Fever, Bronchial Infection.

Data from ClinicalTrials.gov NCT01589302 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Macrophages in immunoregulation and therapeutics.
   Chen S, Saeed AFUH, Liu Q, Jiang Q, et al · · 2023 · cited 1250× · PMID 37211559 · DOI 10.1038/s41392-023-01452-1
2. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia.
   Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, et al · · 2015 · cited 484× · PMID 26182309 · DOI 10.1001/jamaoncol.2014.218
3. Targeting macrophages in cancer immunotherapy.
   Duan Z, Luo Y. · · 2021 · cited 462× · PMID 33767177 · DOI 10.1038/s41392-021-00506-6
4. BTK^C481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia.
   Woyach JA, Ruppert AS, Guinn D, Lehman A, et al · · 2017 · cited 373× · PMID 28418267 · DOI 10.1200/jco.2016.70.2282
5. Ibrutinib treatment improves T cell number and function in CLL patients.
   Long M, Beckwith K, Do P, Mundy BL, et al · · 2017 · cited 306× · PMID 28714866 · DOI 10.1172/jci89756
6. Ventricular arrhythmias and sudden death in patients taking ibrutinib.
   Lampson BL, Yu L, Glynn RJ, Barrientos JC, et al · · 2017 · cited 165× · PMID 28223277 · DOI 10.1182/blood-2016-10-742437
7. Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling.
   Yeh YY, Ozer HG, Lehman AM, Maddocks K, et al · · 2015 · cited 132× · PMID 25833959 · DOI 10.1182/blood-2014-12-618470
8. Cells, cytokines, chemokines, and cancer stress: A biobehavioral study of patients with chronic lymphocytic leukemia.
   Andersen BL, Goyal NG, Weiss DM, Westbrook TD, et al · · 2018 · cited 22× · PMID 29757455 · DOI 10.1002/cncr.31538