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

NCT ID: NCT01855750

Last Updated: 2025-02-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

838 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-03

Study Completion Date

2019-04-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a randomized (individuals assigned to study treatment by chance), double-blind (individuals and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to compare the efficacy and safety of ibrutinib in combination with R-CHOP versus R-CHOP alone in adult patients newly diagnosed non-GCB DLBCL selected by IHC or newly diagnosed patients with ABC subtype of DLBCL identified by GEP or both populations. The study will include screening, active treatment, and posttreatment follow-up phases. The study will end when 50% of participants have died or 5 years after the last participant is randomized or the sponsor terminates the study, whichever occurs first. Approximately 800 participants will be randomly assigned in a 1:1 ratio to receive either placebo+R-CHOP (treatment arm A) or ibrutinib+R-CHOP (treatment arm B). All participants will receive R-CHOP as background therapy for 6 or 8 cycles (21 days per cycle) prespecified according to local practice. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive disease or relapsed disease after complete response will be discontinued from treatment. Participants who discontinue R-CHOP without disease progression will continue study drug (placebo or ibrutinib) until 6 or 8 cycles are completed, disease progression, or unacceptable toxicity, whichever occurs first. After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant Lymphoma. Participants with documented residual disease upon completion of at least 6 cycles of R-CHOP therapy are considered eligible to initiate subsequent antilymphoma therapy. Serial pharmacokinetic samples will be collected before and after dosing, and safety will be monitored throughout the study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment Arm A: placebo + R-CHOP

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

4 matched capsules administered by mouth once daily (21-day cycles)

Rituximab

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Doxorubicin

Intervention Type DRUG

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

Vincristine

Intervention Type DRUG

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

Prednisone (or equivalent)

Intervention Type DRUG

100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Treatment Arm B: ibrutinib + R-CHOP

Treatment Arm B = ibrutinib + R-CHOP

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

560 mg capsules administered by mouth once daily (21-day cycles)

Rituximab

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Doxorubicin

Intervention Type DRUG

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

Vincristine

Intervention Type DRUG

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

Prednisone (or equivalent)

Intervention Type DRUG

100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Ibrutinib

560 mg capsules administered by mouth once daily (21-day cycles)

Intervention Type DRUG

Placebo

4 matched capsules administered by mouth once daily (21-day cycles)

Intervention Type DRUG

Rituximab

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Doxorubicin

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

Intervention Type DRUG

Vincristine

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

Intervention Type DRUG

Prednisone (or equivalent)

100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Pharmacyclics LLC.

INDUSTRY

Sponsor Role collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Osaka, , Japan

Site Status

Tucson, Arizona, United States

Site Status

Greenbrae, California, United States

Site Status

La Jolla, California, United States

Site Status

Los Angeles, California, United States

Site Status

Salinas, California, United States

Site Status

Stanford, California, United States

Site Status

Danbury, Connecticut, United States

Site Status

Hartford, Connecticut, United States

Site Status

Washington D.C., District of Columbia, United States

Site Status

Atlanta, Georgia, United States

Site Status

Marietta, Georgia, United States

Site Status

Peoria, Illinois, United States

Site Status

Fort Wayne, Indiana, United States

Site Status

Goshen, Indiana, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Topeka, Kansas, United States

Site Status

Louisville, Kentucky, United States

Site Status

Baton Rouge, Louisiana, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Baltimore, Maryland, United States

Site Status

Bethesda, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Ann Arbor, Michigan, United States

Site Status

St Louis, Missouri, United States

Site Status

Omaha, Nebraska, United States

Site Status

Hackensack, New Jersey, United States

Site Status

New Brunswick, New Jersey, United States

Site Status

Fresh Meadows, New York, United States

Site Status

Johnson City, New York, United States

Site Status

Mineola, New York, United States

Site Status

New York, New York, United States

Site Status

Rochester, New York, United States

Site Status

The Bronx, New York, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Greenville, North Carolina, United States

Site Status

Hickory, North Carolina, United States

Site Status

Columbus, Ohio, United States

Site Status

Portland, Oregon, United States

Site Status

North Charleston, South Carolina, United States

Site Status

Nashville, Tennessee, United States

Site Status

Houston, Texas, United States

Site Status

Temple, Texas, United States

Site Status

Burlington, Vermont, United States

Site Status

Seattle, Washington, United States

Site Status

Buenos Aires, , Argentina

Site Status

Ciudad de Buenos Aires, , Argentina

Site Status

Adelaide, , Australia

Site Status

Concord, , Australia

Site Status

Darlinghurst, , Australia

Site Status

Hobart, , Australia

Site Status

Melbourne, , Australia

Site Status

Nedlands, , Australia

Site Status

Perth, , Australia

Site Status

Randwick, , Australia

Site Status

South Brisbane, , Australia

Site Status

Woolloongabba, , Australia

Site Status

Antwerp, , Belgium

Site Status

Bruges, , Belgium

Site Status

Brussels, , Belgium

Site Status

Ghent, , Belgium

Site Status

Haine Saint Paul La Louviere, , Belgium

Site Status

Kortrijk, , Belgium

Site Status

Leuven, , Belgium

Site Status

Porto Alegre, , Brazil

Site Status

Rio de Janeiro, , Brazil

Site Status

São Paulo, , Brazil

Site Status

Edmonton, Alberta, Canada

Site Status

Vancouver, British Columbia, Canada

Site Status

Halifax, Nova Scotia, Canada

Site Status

Toronto, Ontario, Canada

Site Status

Lévis, Quebec, Canada

Site Status

Montreal, Quebec, Canada

Site Status

Beijing, , China

Site Status

Changchun, , China

Site Status

Chengdu, , China

Site Status

Guangzhou, , China

Site Status

Hangzhou, , China

Site Status

Harbin, , China

Site Status

Jinan, , China

Site Status

Nanjing, , China

Site Status

Shanghai, , China

Site Status

Tianjin, , China

Site Status

Brno, , Czechia

Site Status

Hradec Králové, , Czechia

Site Status

Ostrava, , Czechia

Site Status

Prague, , Czechia

Site Status

Aarhus N, , Denmark

Site Status

Copenhagen, , Denmark

Site Status

Roskilde, , Denmark

Site Status

Vejle, , Denmark

Site Status

Helsinki, , Finland

Site Status

Jyväskylä, , Finland

Site Status

Oulu, , Finland

Site Status

Turku, , Finland

Site Status

Grenoble, , France

Site Status

Limoges, , France

Site Status

Paris, , France

Site Status

Pessac, , France

Site Status

Pierre-Bénite, , France

Site Status

Rouen, , France

Site Status

Tours, , France

Site Status

Villejuif, , France

Site Status

Augsburg, , Germany

Site Status

Bamberg, , Germany

Site Status

Berlin, , Germany

Site Status

Dresden, , Germany

Site Status

Essen, , Germany

Site Status

Frankfurt, , Germany

Site Status

Jena, , Germany

Site Status

München, , Germany

Site Status

Münster, , Germany

Site Status

Villingen-Schwenningen, , Germany

Site Status

Budapest, , Hungary

Site Status

Debrecen, , Hungary

Site Status

Gyula, , Hungary

Site Status

Szombathely, , Hungary

Site Status

Veszprém, , Hungary

Site Status

Beersheba, , Israel

Site Status

Hadera, , Israel

Site Status

Haifa, , Israel

Site Status

Petah Tikva, , Israel

Site Status

Ramat Gan, , Israel

Site Status

Tel Aviv, , Israel

Site Status

Fukuoka, , Japan

Site Status

Hiroshima, , Japan

Site Status

Isehara, , Japan

Site Status

Kobe, , Japan

Site Status

Kumamoto, , Japan

Site Status

Kyoto, , Japan

Site Status

Nagano, , Japan

Site Status

Nagoya, , Japan

Site Status

Narita, , Japan

Site Status

Ōsaka-sayama, , Japan

Site Status

Sapporo, , Japan

Site Status

Sendai, , Japan

Site Status

Suita, , Japan

Site Status

Tachikawa, , Japan

Site Status

Tokyo, , Japan

Site Status

Tsukuba, , Japan

Site Status

México, , Mexico

Site Status

Monterrey, , Mexico

Site Status

San Luis Potosí City, , Mexico

Site Status

Amsterdam-Zuidoost, , Netherlands

Site Status

Arnhem, , Netherlands

Site Status

Dordrecht, , Netherlands

Site Status

Groningen, , Netherlands

Site Status

Leiden, , Netherlands

Site Status

Nieuwegein, , Netherlands

Site Status

Rotterdam, , Netherlands

Site Status

Oslo, , Norway

Site Status

Tromsø, , Norway

Site Status

Brzozów, , Poland

Site Status

Chorzów, , Poland

Site Status

Krakow, , Poland

Site Status

Lodz, , Poland

Site Status

Olsztyn, , Poland

Site Status

Poznan, , Poland

Site Status

Warsaw, , Poland

Site Status

Wroclaw, , Poland

Site Status

Moscow, , Russia

Site Status

Nizhny Novgorod, , Russia

Site Status

Rostov-on-Don, , Russia

Site Status

Saint Petersburg, , Russia

Site Status

Sochi, , Russia

Site Status

Volgograd, , Russia

Site Status

Yekaterinburg, , Russia

Site Status

Busan, , South Korea

Site Status

Goyang-si, , South Korea

Site Status

Seoul, , South Korea

Site Status

Barcelona, , Spain

Site Status

Madrid, , Spain

Site Status

Salamanca, , Spain

Site Status

Seville, , Spain

Site Status

Linköping, , Sweden

Site Status

Luleå, , Sweden

Site Status

Lund, , Sweden

Site Status

Uppsala, , Sweden

Site Status

Taichung, , Taiwan

Site Status

Tainan City, , Taiwan

Site Status

Taoyuan, , Taiwan

Site Status

Adana, , Turkey (Türkiye)

Site Status

Ankara, , Turkey (Türkiye)

Site Status

Istanbul, , Turkey (Türkiye)

Site Status

Izmir, , Turkey (Türkiye)

Site Status

Kayseri, , Turkey (Türkiye)

Site Status

Samsun, , Turkey (Türkiye)

Site Status

Cherkassy, , Ukraine

Site Status

Khmelnitskiy, , Ukraine

Site Status

Kiev, , Ukraine

Site Status

Lviv, , Ukraine

Site Status

Makiivka, , Ukraine

Site Status

Glasgow, , United Kingdom

Site Status

Liverpool, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Maidstone, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Nottingham, , United Kingdom

Site Status

Oxford, , United Kingdom

Site Status

Romford, , United Kingdom

Site Status

Southampton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Belgium Brazil Canada China Czechia Denmark Finland France Germany Hungary Israel Japan Mexico Netherlands Norway Poland Russia South Korea Spain Sweden Taiwan Turkey (Türkiye) Ukraine United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

Reference Type DERIVED
PMID: 39563886 (View on PubMed)

Johnson PWM, Balasubramanian S, Hodkinson B, Shreeve SM, Sun S, Srinivasan S, Steele AJ, Vermeulen J, Sehn LH, Wilson WH. Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial. Blood Adv. 2023 May 23;7(10):2008-2017. doi: 10.1182/bloodadvances.2022009389.

Reference Type DERIVED
PMID: 36696540 (View on PubMed)

Wilson WH, Wright GW, Huang DW, Hodkinson B, Balasubramanian S, Fan Y, Vermeulen J, Shreeve M, Staudt LM. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL. Cancer Cell. 2021 Dec 13;39(12):1643-1653.e3. doi: 10.1016/j.ccell.2021.10.006. Epub 2021 Nov 4.

Reference Type DERIVED
PMID: 34739844 (View on PubMed)

Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppa S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Duhrsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non-Germinal Center B-Cell Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. doi: 10.1200/JCO.18.02403. Epub 2019 Mar 22.

Reference Type DERIVED
PMID: 30901302 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PCI-32765DBL3001

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1139-6222

Identifier Type: OTHER

Identifier Source: secondary_id

2013-000959-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR102118

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Ibrutinib + R-CHOP Followed by Ibrutinib Maintenance
NCT03731234 ACTIVE_NOT_RECRUITING PHASE2