Clinical Trials List
Protocol NumberPCI-32765MCL3002
NCT Number(ClinicalTrials.gov Identfier)NCT01776840
Completed
2013-03-01 - 2019-10-31
Phase III
Terminated6
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination with Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma
-
Trial Applicant
Johnson & Johnson
-
Sponsor
Janssen Research & Development
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Tsu-Yi Chao Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 何景良 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 高偉堯 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jyh-Pyng Gau Division of Hematology & Oncology
- Tzeon-jye Chiou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Tung-Liang Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- HSIN-AN HOU Division of Hematology & Oncology
- 蔡偉 Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 賴冠銘 Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Mantle Cell Lymphoma
Objectives
Primary Objective
The primary objective of this study is to evaluate whether the addition of ibrutinib to bendamustine and
rituximab will result in prolongation of progression-free survival (PFS) in subjects with newly diagnosed
MCL who are 65 years of age or older.
Secondary Objectives
Secondary objectives include evaluation of overall survival; CR rate; overall response rate (CR+ partial
response [PR]); patient-reported lymphoma symptoms and concerns as measured by the lymphoma (Lym)
subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym); minimal residual
disease (MRD) negative rate; duration of response; time-to-next treatment (TTNT); safety of ibrutinib
when combined with BR; and to characterize the pharmacokinetics of ibrutinib and explore the potential
relationships between ibrutinib metrics of exposure with relevant clinical, pharmacodynamic, or
biomarker information.
Test Drug
Ibrutinib
Active Ingredient
Ibrutinib
Dosage Form
Capsules
Dosage
140
Endpoints
The primary endpoint of PFS has served as the basis for regulatory approvals in MCL. The
secondary endpoint, overall survival, is a gold standard endpoint for the clinical evaluation of
new treatments.
secondary endpoint, overall survival, is a gold standard endpoint for the clinical evaluation of
new treatments.
Inclution Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. Subject is 65 years of age or older
2. Diagnosis of MCL must include morphology and expression of either cyclin D1 in
association with one B-cell marker (eg, CD19, CD20, or PAX5) and CD5 or evidence of
t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase
chain reaction (PCR) (see Section 9.1.2).
- A report from the local laboratory is acceptable; however, it must be reviewed and
approved by the central pathology laboratory to verify the above criteria prior to
randomization. The formalin-fixed paraffin-embedded tumor tissue (FFPE) block or
slides must be sent to the central laboratory for final confirmation of MCL diagnosis
after randomization.
- If the report from the local laboratory is not available prior to randomization, the tumor
block or slides must be sent to the central pathology laboratory for confirmation of
MCL diagnosis.
3. Clinical Stage II, III, or IV by Ann Arbor Classification (see Attachment 1)
4. 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 dimensions9
5. No prior therapies for MCL
6. Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
(Attachment 2)
7. Hematology values must be within the following limits within 14 days prior to
randomization:
a. Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support
b. Platelets ≥ 100,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of
transfusion support in either situation
8. Biochemical values within the following limits within 14 days prior to randomization:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper
limit of normal (ULN)
b. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of nonhepatic origin
c. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft-Gault11)
≥ 40 mL/min/1.73m2
9. 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 females, these
restrictions apply for 6 months after last dose of bendamustine, 12 months after the last dose
of rituximab, or 1 month after the last dose of study drug, whichever is later. For males,
these restrictions apply for 6 months after the last dose of bendamustine, 12 months after the
last dose of rituximab, or 3 months after the last dose of study drug, whichever is later.
10. Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
breastfeeding are ineligible for this study.
11. Sign (or their legally-acceptable representatives must sign) an informed consent document
indicating that they understand the purpose of and procedures required for the study,
including biomarkers, and are willing to participate in the study.
1. Subject is 65 years of age or older
2. Diagnosis of MCL must include morphology and expression of either cyclin D1 in
association with one B-cell marker (eg, CD19, CD20, or PAX5) and CD5 or evidence of
t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase
chain reaction (PCR) (see Section 9.1.2).
- A report from the local laboratory is acceptable; however, it must be reviewed and
approved by the central pathology laboratory to verify the above criteria prior to
randomization. The formalin-fixed paraffin-embedded tumor tissue (FFPE) block or
slides must be sent to the central laboratory for final confirmation of MCL diagnosis
after randomization.
- If the report from the local laboratory is not available prior to randomization, the tumor
block or slides must be sent to the central pathology laboratory for confirmation of
MCL diagnosis.
3. Clinical Stage II, III, or IV by Ann Arbor Classification (see Attachment 1)
4. 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 dimensions9
5. No prior therapies for MCL
6. Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
(Attachment 2)
7. Hematology values must be within the following limits within 14 days prior to
randomization:
a. Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support
b. Platelets ≥ 100,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of
transfusion support in either situation
8. Biochemical values within the following limits within 14 days prior to randomization:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper
limit of normal (ULN)
b. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of nonhepatic origin
c. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft-Gault11)
≥ 40 mL/min/1.73m2
9. 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 females, these
restrictions apply for 6 months after last dose of bendamustine, 12 months after the last dose
of rituximab, or 1 month after the last dose of study drug, whichever is later. For males,
these restrictions apply for 6 months after the last dose of bendamustine, 12 months after the
last dose of rituximab, or 3 months after the last dose of study drug, whichever is later.
10. Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
breastfeeding are ineligible for this study.
11. Sign (or their legally-acceptable representatives must sign) an informed consent document
indicating that they understand the purpose of and procedures required for the study,
including biomarkers, 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 lymphoma.
3. Diagnosed or treated for malignancy other than MCL, 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 cervical carcinoma in situ without evidence of disease.
4. Subjects for whom the goal of therapy is tumor debulking prior to stem cell transplant.
5. History of stroke or intracranial hemorrhage within 6 months prior to randomization.
6. Requires anticoagulation with warfarin or equivalent vitamin K antagonists
(eg, phenprocoumon).
7. Requires treatment with strong CYP3A4/5 inhibitors.
8. 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.
9. Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
10. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or
active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (IV) antibiotics.
11. 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.
1. Major surgery within 4 weeks of randomization.
2. Known central nervous system lymphoma.
3. Diagnosed or treated for malignancy other than MCL, 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 cervical carcinoma in situ without evidence of disease.
4. Subjects for whom the goal of therapy is tumor debulking prior to stem cell transplant.
5. History of stroke or intracranial hemorrhage within 6 months prior to randomization.
6. Requires anticoagulation with warfarin or equivalent vitamin K antagonists
(eg, phenprocoumon).
7. Requires treatment with strong CYP3A4/5 inhibitors.
8. 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.
9. Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
10. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or
active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (IV) antibiotics.
11. 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
-
Taiwan
16 participants
-
Global
520 participants
