Clinical Trials List
Protocol NumberPCI-32765DBL3001
NCT Number(ClinicalTrials.gov Identfier)NCT01855750
2013-09-01 - 2019-03-08
Phase III
Terminated3
Study ended1
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
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Trial Applicant
Johnson & Johnson
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Sponsor
Janssen Research & Development
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Tung-Liang Lin Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Ching Yun Hsieh Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
9 Study ended
Co-Principal Investigator
- Yu-Min Yeh Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Diffuse Large B-Cell Lymphoma(DLBCL)
Objectives
Primary Objective
To evaluate if the addition of ibrutinib to R-CHOP prolongs event-free survival (EFS) compared with
R-CHOP alone in subjects with newly diagnosed non-GCB DLBCL.
Secondary Objectives
To compare ibrutinib in combination with R-CHOP versus R-CHOP alone with regard to progression-free
survival (PFS), overall survival, complete response [CR] rate, patient-reported lymphoma symptoms and
concerns, treatment benefit of ibrutinib in subjects with the ABC subtype based on gene expression
profiling (GEP), and safety. Additional secondary objectives are to characterize the pharmacokinetics of
ibrutinib and explore the potential relationships between ibrutinib metrics of exposure with relevant
clinical or biomarker information.
Test Drug
Ibrutinib
Active Ingredient
Ibrutinib
Dosage Form
Capsule
Dosage
140
Endpoints
Primary Endpoint
The primary endpoint is EFS, defined as the duration from the date of randomization to the date
of disease progression, relapse from CR as assessed by the investigator, initiation of subsequent
systemic antilymphoma therapy for either PET-positive or biopsy-proven residual disease upon
completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first. Refer to the
Statistical Analysis Plan for further details regarding censoring rules.
Secondary Endpoint(s)
The secondary endpoints are defined as follows:
Progression-free survival is defined as the duration from the date of randomization to the
date of progression, relapse from CR, or death, whichever occurs first.
Overall survival is defined as the duration from the date of randomization to the date of the
subject’s death. If the subject is alive or the vital status is unknown, then the subject will be
censored at the date the subject was last known to be alive.
CR rate is defined as the proportion of subjects with measurable disease who achieve CR.
Time to worsening in the Lym subscale of the FACT-Lym is defined as the time from the
date of randomization to the start date of the worsening of patient symptoms. Worsening is
defined by a 5-point decrease from baseline in patient symptoms.
Pharmacokinetic parameters (eg, oral plasma clearance [CL/F], oral volume of distribution
at steady state [Vss/F]) or metrics of systemic exposure (eg, AUC, minimum observed
plasma concentration [Cmin]) of ibrutinib after oral daily dosing in a subset of subjects.
Parameters describing the potential relationships between ibrutinib metrics of exposure with
relevant clinical, or biomarker information.
Safety parameters of ibrutinib when combined with R-CHOP.
The primary endpoint is EFS, defined as the duration from the date of randomization to the date
of disease progression, relapse from CR as assessed by the investigator, initiation of subsequent
systemic antilymphoma therapy for either PET-positive or biopsy-proven residual disease upon
completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first. Refer to the
Statistical Analysis Plan for further details regarding censoring rules.
Secondary Endpoint(s)
The secondary endpoints are defined as follows:
Progression-free survival is defined as the duration from the date of randomization to the
date of progression, relapse from CR, or death, whichever occurs first.
Overall survival is defined as the duration from the date of randomization to the date of the
subject’s death. If the subject is alive or the vital status is unknown, then the subject will be
censored at the date the subject was last known to be alive.
CR rate is defined as the proportion of subjects with measurable disease who achieve CR.
Time to worsening in the Lym subscale of the FACT-Lym is defined as the time from the
date of randomization to the start date of the worsening of patient symptoms. Worsening is
defined by a 5-point decrease from baseline in patient symptoms.
Pharmacokinetic parameters (eg, oral plasma clearance [CL/F], oral volume of distribution
at steady state [Vss/F]) or metrics of systemic exposure (eg, AUC, minimum observed
plasma concentration [Cmin]) of ibrutinib after oral daily dosing in a subset of subjects.
Parameters describing the potential relationships between ibrutinib metrics of exposure with
relevant clinical, or biomarker information.
Safety parameters of ibrutinib when combined with R-CHOP.
Inclution Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. Subject must be 18 years of age or older
2. No prior treatment for DLBCL.
3. Histologically-confirmed non-GCB DLBCL
– The histological confirmation of DLBCL will be based on central review of the local
pathology report.
– Paraffin-embedded tumor tissue must be sent to the central laboratory for determination
of the non-GCB subtype by IHC prior to randomization (Attachment 2).
4. Stage II (not candidates for local X-ray therapy), III, or IV disease by the Ann Arbor
Classification
5. At least 1 measurable site of disease according to Revised Response Criteria for Malignant
Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of
short axis measurement or greater than 1.0 cm in the short axis regardless of long axis
measurement, and clearly measurable in 2 perpendicular dimensions.
6. R-IPI score of 1 (Attachment 1)
7. Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2 (Attachment 3)
8. Hematology values must be within the following limits within 14 days prior to
randomization and at baseline:
a. Absolute neutrophil count (ANC) 1,000 cells/μL unless if bone marrow involvement
b. Platelets 75,000 cells/μL unless if bone marrow involvement.
9. Biochemical values must be within the following limits within 14 days prior to
randomization and at baseline:
a. Alanine aminotransferase (ALT) 3 x upper limit of normal (ULN). Aspartate
aminotransferase (AST) 3 x ULN.
b. Total bilirubin ≤1.5 x ULN, unless bilirubin rise is due to Gilbert’s syndrome or of
non-hepatic origin
c. Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate
≥40 mL/min/1.73m2
10. LVEF within institutional normal limits, as determined by echocardiography or multiple
uptake gated acquisition (MUGA) scan.
11. Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with local
regulations regarding the use of birth control methods for subjects participating in clinical
trials. Men must agree to not donate sperm during and after the study. For women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose
of study drug, whichever is later. For men, these restrictions apply for 12 months after the
last dose of rituximab or 3 months after the last dose of study drug, whichever is later.
12. Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
breastfeeding are ineligible for this study.
13. Each subject (or their legally acceptable representative) must sign an informed consent form
(ICF) indicating that he or she understands the purpose of and procedures required for the
study and are willing to participate in the study.
1. Subject must be 18 years of age or older
2. No prior treatment for DLBCL.
3. Histologically-confirmed non-GCB DLBCL
– The histological confirmation of DLBCL will be based on central review of the local
pathology report.
– Paraffin-embedded tumor tissue must be sent to the central laboratory for determination
of the non-GCB subtype by IHC prior to randomization (Attachment 2).
4. Stage II (not candidates for local X-ray therapy), III, or IV disease by the Ann Arbor
Classification
5. At least 1 measurable site of disease according to Revised Response Criteria for Malignant
Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of
short axis measurement or greater than 1.0 cm in the short axis regardless of long axis
measurement, and clearly measurable in 2 perpendicular dimensions.
6. R-IPI score of 1 (Attachment 1)
7. Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2 (Attachment 3)
8. Hematology values must be within the following limits within 14 days prior to
randomization and at baseline:
a. Absolute neutrophil count (ANC) 1,000 cells/μL unless if bone marrow involvement
b. Platelets 75,000 cells/μL unless if bone marrow involvement.
9. Biochemical values must be within the following limits within 14 days prior to
randomization and at baseline:
a. Alanine aminotransferase (ALT) 3 x upper limit of normal (ULN). Aspartate
aminotransferase (AST) 3 x ULN.
b. Total bilirubin ≤1.5 x ULN, unless bilirubin rise is due to Gilbert’s syndrome or of
non-hepatic origin
c. Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate
≥40 mL/min/1.73m2
10. LVEF within institutional normal limits, as determined by echocardiography or multiple
uptake gated acquisition (MUGA) scan.
11. Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with local
regulations regarding the use of birth control methods for subjects participating in clinical
trials. Men must agree to not donate sperm during and after the study. For women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose
of study drug, whichever is later. For men, these restrictions apply for 12 months after the
last dose of rituximab or 3 months after the last dose of study drug, whichever is later.
12. Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
breastfeeding are ineligible for this study.
13. Each subject (or their legally acceptable representative) must sign an informed consent form
(ICF) indicating that he or she understands the purpose of and procedures required for the
study and are willing to participate in the study.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study.
1. Major surgery within 4 weeks of randomization
2. Known central nervous system (CNS) lymphoma
3. Known primary mediastinal lymphoma
4. Prior history of indolent lymphoma
5. Diagnosed or treated for malignancy other than DLBCL, except:
a. Malignancy treated with curative intent and with no known active disease present for
≥3 years before randomization
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
c. Adequately treated carcinoma in situ without evidence of disease
6. History of stroke or intracranial hemorrhage within 6 months prior to randomization
7. Requires anticoagulation with warfarin or equivalent vitamin K antagonists
(eg, phenprocoumon)
8. Requires treatment with strong CYP3A4/5 inhibitors
9. Prior anthracycline use 150 mg/m2
10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the
New York Heart Association Functional Classification
11. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus (HCV;
RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B Virus (HBV; DNA
PCR-positive) infection or any uncontrolled active systemic infection requiring intravenous
(IV) antibiotics. Subjects with PCR-negative HBV are permitted in the study.
12. Any 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 ibrutinib capsules, or put the study outcomes at undue risk
in the study.
1. Major surgery within 4 weeks of randomization
2. Known central nervous system (CNS) lymphoma
3. Known primary mediastinal lymphoma
4. Prior history of indolent lymphoma
5. Diagnosed or treated for malignancy other than DLBCL, except:
a. Malignancy treated with curative intent and with no known active disease present for
≥3 years before randomization
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
c. Adequately treated carcinoma in situ without evidence of disease
6. History of stroke or intracranial hemorrhage within 6 months prior to randomization
7. Requires anticoagulation with warfarin or equivalent vitamin K antagonists
(eg, phenprocoumon)
8. Requires treatment with strong CYP3A4/5 inhibitors
9. Prior anthracycline use 150 mg/m2
10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the
New York Heart Association Functional Classification
11. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus (HCV;
RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B Virus (HBV; DNA
PCR-positive) infection or any uncontrolled active systemic infection requiring intravenous
(IV) antibiotics. Subjects with PCR-negative HBV are permitted in the study.
12. Any 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 ibrutinib capsules, or put the study outcomes at undue risk
The Estimated Number of Participants
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Taiwan
17 participants
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Global
800 participants
