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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01855750




Registration number
NCT01855750
Ethics application status
Date submitted
14/05/2013
Date registered
16/05/2013
Date last updated
13/04/2020

Titles & IDs
Public title
A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Scientific title
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
Secondary ID [1] 0 0
PCI-32765DBL3001
Secondary ID [2] 0 0
CR102118
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Placebo
Treatment: Drugs - Rituximab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone (or equivalent)

Placebo Comparator: Treatment Arm A: placebo + R-CHOP - Treatment Arm A = placebo + R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)

Experimental: Treatment Arm B: ibrutinib + R-CHOP - Treatment Arm B = ibrutinib + R-CHOP


Treatment: Drugs: Ibrutinib
560 mg capsules administered by mouth once daily (21-day cycles)

Treatment: Drugs: Placebo
4 matched capsules administered by mouth once daily (21-day cycles)

Treatment: Drugs: Rituximab
375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Treatment: Drugs: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Treatment: Drugs: Doxorubicin
50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Treatment: Drugs: Vincristine
1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Treatment: Drugs: Prednisone (or equivalent)
100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population
Timepoint [1] 0 0
Up to 5.5 years
Primary outcome [2] 0 0
Event-Free Survival (EFS) - Activated B-Cell (ABC) Population
Timepoint [2] 0 0
Up to approximately 4.5 years
Secondary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 4.5 years
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved Complete Response (CR)
Timepoint [2] 0 0
Up to approximately 4.5 years
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Up to 5.5 years
Secondary outcome [4] 0 0
Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
Timepoint [4] 0 0
Up to approximately 4.5 years

Eligibility
Key inclusion criteria
- No prior treatment for diffuse B-cell lymphoma (DLBCL)

- Histologically-confirmed non-germinal center B-cell subtype DLBCL

- Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor
Classification

- At least 1 measurable site of disease according to Revised Response Criteria for
Malignant Lymphoma

- Revised International Prognostic Index score of >=1

- Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2

- Hematology and biochemical laboratory values within protocol-defined parameters prior
to random assignment and at baseline

- Left ventricular ejection fraction within institutional normal limits, as determined
by echocardiography or multiple uptake gated acquisition (MUGA) scan

- Agrees to protocol-defined use of effective contraception (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)

- Men must agree to not donate sperm during and after the study for 12 months after the
last dose of rituximab or 3 months after the last dose of study drug, whichever is
later

- Women of childbearing potential must have a negative serum or urine pregnancy test at
screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Major surgery within 4 weeks of random assignment

- Known central nervous system or primary mediastinal lymphoma

- Prior history of indolent lymphoma

- Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with
curative intent and with no known active disease present for >=3 years before random
assignment; adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease; adequately treated carcinoma in situ without evidence of disease

- History of stroke or intracranial hemorrhage within 6 months prior to random
assignment

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists

- Requires treatment with strong CYP3A inhibitors

- Prior anthracycline use >=150 mg/m2

- 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

- Known history of human immunodeficiency virus or active hepatitis C virus or active
hepatitis B virus infection or any uncontrolled active systemic infection requiring
intravenous antibiotics

- Women who are pregnant or breastfeeding

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the patient's safety, interfere with the
absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/04/2019
Sample size
Target
Accrual to date
Final
838
Recruitment in Australia
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- Adelaide
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- Concord
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- Darlinghurst
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- Nedlands
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- Perth
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- Randwick
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- South Brisbane
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- Woolloongabba
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- Adelaide
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- Concord
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- Darlinghurst
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- Hobart
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- Melbourne
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- Nedlands
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- Perth
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- Randwick
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- South Brisbane
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- Woolloongabba
Recruitment outside Australia
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Russian Federation
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Russian Federation
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Russian Federation
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Sochi
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Russian Federation
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Adana
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Ankara
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Istanbul
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Izmir
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Kayseri
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Samsun
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Ukraine
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Cherkassy
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Ukraine
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Khmelnitskiy
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Ukraine
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Kiev
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Ukraine
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Lviv
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Ukraine
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Makiivka
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United Kingdom
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Glasgow
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United Kingdom
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Liverpool
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United Kingdom
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London
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United Kingdom
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Maidstone
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United Kingdom
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Manchester
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Nottingham
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Oxford
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Romford
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Pharmacyclics LLC.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate if ibrutinib administered in combination with
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the
clinical outcome in newly diagnosed patients with non-germinal center B-cell subtype (GCB) of
diffuse large B-cell lymphoma (DLBCL) selected by immunohistochemistry (IHC) or newly
diagnosed patients with activated B cell-like (ABC) subtype of DLBCL identified by gene
expression profiling (GEP) or both populations.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01855750
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01855750