A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Treated Indolent Non-Hodgkin Lymphoma

Overview[ - collapse ][ - ]

Purpose The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered in combination with either bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in adult patients with previously treated indolent Non-Hodgkin lymphoma.
ConditionLymphoma
InterventionDrug: Bendamustine
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: PCI-32765 (Ibrutinib)
Drug: Placebo
PhasePhase 3
SponsorJanssen Research & Development, LLC
Responsible PartyJanssen Research & Development, LLC
ClinicalTrials.gov IdentifierNCT01974440
First ReceivedOctober 28, 2013
Last UpdatedApril 16, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateOctober 28, 2013
Last Updated DateApril 16, 2014
Start DateJanuary 2014
Estimated Primary Completion DateAugust 2021
Current Primary Outcome MeasuresProgression-free survival [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Overall survival [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
  • Complete response rate [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
  • Overall response rate [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
  • Duration of response [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
  • Participants with change in patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [Time Frame: Up to approximately 7 years after the first participant is randomized] [Designated as safety issue: No]
  • Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) [Time Frame: Up to 30 days after the last dose of study medication] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleA Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Treated Indolent Non-Hodgkin Lymphoma
Official TitleA Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Either Bendamustine and Rituximab (BR) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Previously Treated Indolent Non-Hodgkin Lymphoma (iNHL)
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib)
administered in combination with either bendamustine and rituximab (BR) or rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in adult patients with
previously treated indolent Non-Hodgkin lymphoma.
Detailed Description
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 in approximately 400 adult patients with
follicular lymphoma or marginal zone lymphoma. The study will include the following phases:
screening, treatment, and a posttreatment follow-up. Eligible patients will be randomly
assigned in a 1:1 ratio to either treatment Arm A (background immune-chemotherapy + placebo)
or treatment Arm B (background immune-chemotherapy + 560 mg of ibrutinib). All participants
will receive 6 cycles of background immune-chemotherapy with either BR or R-CHOP in
combination with either placebo (Arm A) or ibrutinib (Arm B). Selection of background
immune-chemotherapy will be based on prior treatment history and cardiac function. After
completion of background immune-chemotherapy, study drug (ibrutinib or placebo) will
continue until disease progression, unacceptable toxicity, or study end. Assessment of tumor
response and progression will be conducted in accordance with the Revised Response Criteria
for Malignant Lymphoma. Serial pharmacokinetic (study of what a drug does to the body) blood
samples will be collected. Safety will be assessed throughout the study.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionLymphoma
InterventionDrug: Bendamustine
90 mg/m2 administered intravenously on Days 1-2
Drug: Rituximab
375 mg/m2 administered intravenously on Day 1
Drug: Cyclophosphamide
750 mg/m2 administered intravenously on Day 1
Drug: Doxorubicin
50 mg/m2 administered intravenously on Day 1
Drug: Vincristine
1.4 mg/m2 (maximum total 2 mg) administered intravenously on Day 1
Drug: Prednisone
100 mg administered orally on Days 1-5
Drug: PCI-32765 (Ibrutinib)
560 mg capsules administered by mouth once daily, continuously starting on Cycle 1, Day 1
Drug: Placebo
Matched to study drug administered by mouth once daily, continuously starting on Cycle 1, Day 1
Study Arm (s)
  • Placebo Comparator: Treatment Arm A
    Treatment Arm A = background immune-chemotherapy (bendamustine and rituximab [BR] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for 6 cycles + placebo
  • Experimental: Treatment Arm B
    Treatment Arm B = background immune-chemotherapy (BR or R-CHOP) for 6 cycles + PCI-32765 (Ibrutinib)

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment400
Estimated Completion DateAugust 2021
Estimated Primary Completion DateOctober 2017
Eligibility Criteria
Inclusion Criteria:

- Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with
histological subtype limited to follicular lymphoma or marginal zone lymphoma

- At least 1 prior treatment with a CD20 antibody combination chemotherapy regimen

- Disease that has relapsed or was refractory after prior chemoimmunotherapy

- At least 1 measurable site of disease according to Revised Response Criteria for
Malignant Lymphoma 2007

- Eastern Cooperative Oncology Group performance status grade 0 or 1

- Laboratory values within protocol-defined parameters

- Agrees to protocol-defined use of effective contraception

- Men must agree not to donate sperm during and after the study 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 medication, whichever is later

- Women of childbearing potential must have a negative serum or urine pregnancy test at
screening

Exclusion Criteria:

- Prior treatment according to protocol-defined criteria

- Unable to receive background chemotherapy based on prior treatment history and
cardiac function

- Known central nervous system lymphoma

- Diagnosed or treated for malignancy other than indolent Non-Hodgkin lymphoma

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

- Requires anticoagulation with warfarin or equivalent Vitamin K antagonists or
treatment with strong CYP3A4/5 inhibitors

- Clinically significant cardiovascular disease

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

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

- Women who are pregnant or breastfeeding
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:
JNJ.CT@sylogent.com
Location CountriesUnited States, Argentina, Australia, Belgium, Brazil, France, Germany, Israel, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT01974440
Other Study ID NumbersCR102786
Has Data Monitoring CommitteeYes
Information Provided ByJanssen Research & Development, LLC
Study SponsorJanssen Research & Development, LLC
CollaboratorsPharmacyclics
Investigators Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Verification DateApril 2014

Locations[ + expand ][ + ]

United States, Alabama
Birmingham, Alabama, United States
Withdrawn
United States, Alabama
Huntsville, Alabama, United States
Withdrawn
United States, Arizona
Gilbert, Arizona, United States
Not yet recruiting
United States, Arkansas
Fayetteville, Arkansas, United States
Withdrawn
United States, California
La Jolla, California, United States
Not yet recruiting
United States, California
San Diego, California, United States
Withdrawn
United States, California
Stanford, California, United States
Suspended
United States, Colorado
Aurora, Colorado, United States
Withdrawn
United States, District of Columbia
Washington, District of Columbia, United States
Withdrawn
United States, Florida
Ocala, Florida, United States
Recruiting
United States, Florida
Orlando, Florida, United States
Withdrawn
United States, Georgia
Atlanta, Georgia, United States
Not yet recruiting
United States, Illinois
Chicago, Illinois, United States
Not yet recruiting
United States, Illinois
Springfield, Illinois, United States
Withdrawn
United States, Indiana
Indianapolis, Indiana, United States
Not yet recruiting
United States, Iowa
Sioux City, Iowa, United States
Withdrawn
United States, Kansas
Westwood, Kansas, United States
Not yet recruiting
United States, Kentucky
Lexington, Kentucky, United States
Not yet recruiting
United States, Kentucky
Louisville, Kentucky, United States
Withdrawn
United States, Louisiana
Baton Rouge, Louisiana, United States
Withdrawn
United States, Louisiana
Lafayette, Louisiana, United States
Not yet recruiting
United States, Louisiana
Marrero, Louisiana, United States
Withdrawn
United States, Maine
Scarborough, Maine, United States
Not yet recruiting
United States, Maryland
Baltimore, Maryland, United States
Withdrawn
United States, Maryland
Baltimore, Maryland, United States
Not yet recruiting
United States, Maryland
Bethesda, Maryland, United States
Not yet recruiting
United States, Massachusetts
Boston, Massachusetts, United States
Not yet recruiting
United States, Michigan
Battle Creek, Michigan, United States
Recruiting
United States, Michigan
Detroit, Michigan, United States
Not yet recruiting
United States, Michigan
Detroit, Michigan, United States
Withdrawn
United States, New Jersey
Denville, New Jersey, United States
Not yet recruiting
United States, New Jersey
Newark, New Jersey, United States
Not yet recruiting
United States, New York
New York, New York, United States
Not yet recruiting
United States, North Carolina
Greenville, North Carolina, United States
Withdrawn
United States, North Carolina
Hickory, North Carolina, United States
Recruiting
United States, North Carolina
Pinehurst, North Carolina, United States
Not yet recruiting
United States, North Dakota
Bismarck, North Dakota, United States
Not yet recruiting
United States, North Dakota
Fargo, North Dakota, United States
Not yet recruiting
United States, Oregon
Bend, Oregon, United States
Not yet recruiting
United States, Oregon
Portland, Oregon, United States
Withdrawn
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
Not yet recruiting
United States, South Carolina
Spartanburg, South Carolina, United States
Not yet recruiting
United States, South Dakota
Sioux Falls, South Dakota, United States
Not yet recruiting
United States, Texas
Houston, Texas, United States
Not yet recruiting
United States, Texas
Lubbock, Texas, United States
Not yet recruiting
United States, Vermont
Burlington, Vermont, United States
Withdrawn
United States, Washington
Spokane, Washington, United States
Not yet recruiting
Argentina
Buenos Aires, Argentina
Withdrawn
Argentina
Buenos Aires, Argentina
Not yet recruiting
Argentina
Ciudad Autonoma Buenos Aires, Argentina
Not yet recruiting
Argentina
Ciudad De Buenos Aires, Argentina
Withdrawn
Argentina
Cordoba, Argentina
Withdrawn
Argentina
La Capital, Argentina
Not yet recruiting
Argentina
Mendoza, Argentina
Not yet recruiting
Argentina
Santa Fe, Argentina
Not yet recruiting
Australia
Adelaide, Australia
Recruiting
Australia
Fitzroy, Australia
Not yet recruiting
Australia
Heidelberg, Australia
Recruiting
Australia
South Brisbane, Australia
Recruiting
Australia
Sydney, Australia
Not yet recruiting
Australia
Wahroonga, Australia
Not yet recruiting
Belgium
Brussel, Belgium
Not yet recruiting
Belgium
Edegem, Belgium
Not yet recruiting
Belgium
Gent, Belgium
Not yet recruiting
Belgium
Leuven, Belgium
Recruiting
Belgium
Namur, Belgium
Recruiting
Belgium
Wilrijk, Belgium
Not yet recruiting
Brazil
Porto Alegre, Brazil
Not yet recruiting
Brazil
Rio De Janeiro, Brazil
Not yet recruiting
Brazil
Salvador, Brazil
Not yet recruiting
Brazil
Sao Paulo, Brazil
Not yet recruiting
France
Montpellier, France
Suspended
France
Nice Cedex 2, France
Recruiting
France
Paris, France
Not yet recruiting
France
Pessac, France
Recruiting
France
Pierre Benite, France
Recruiting
France
Rennes, France
Not yet recruiting
Germany
Berlin, Germany
Not yet recruiting
Germany
Chemnitz, Germany
Withdrawn
Germany
Gießen, Germany
Not yet recruiting
Germany
Göttingen, Germany
Not yet recruiting
Germany
Heidelberg, Germany
Withdrawn
Germany
Ludwigshafen, Rp, Germany
Not yet recruiting
Germany
Magdeburg, Germany
Not yet recruiting
Germany
Mainz, Germany
Not yet recruiting
Germany
Munchen, Germany
Not yet recruiting
Germany
Wiesbaden, Germany
Not yet recruiting
Israel
Afula, Israel
Withdrawn
Israel
Haifa, Israel
Recruiting
Israel
Haifa, Israel
Not yet recruiting
Israel
Jerusalem, Israel
Not yet recruiting
Israel
Nahariya, Israel
Not yet recruiting
Israel
Netanya, Israel
Not yet recruiting
Israel
Petah Tikva, Israel
Recruiting
Israel
Tel Aviv, Israel
Withdrawn
Japan
Fukuoka, Japan
Withdrawn
Japan
Hiroshima, Japan
Not yet recruiting
Japan
Isehara, Japan
Not yet recruiting
Japan
Nagoya, Japan
Not yet recruiting
Japan
Osaka, Japan
Withdrawn
Japan
Osaka, Japan
Not yet recruiting
Japan
Osaka-Sayama, Japan
Not yet recruiting
Japan
Sapporo, Japan
Recruiting
Japan
Sendai, Japan
Not yet recruiting
Japan
Tokyo, Japan
Not yet recruiting
Korea, Republic of
Hwasun Gun, Korea, Republic of
Not yet recruiting
Korea, Republic of
Seoul, Korea, Republic of
Not yet recruiting
Korea, Republic of
Seoul, Korea, Republic of
Recruiting
Poland
Gdynia, Poland
Not yet recruiting
Poland
Olsztyn, Poland
Not yet recruiting
Poland
Warszawa, Poland
Not yet recruiting
Puerto Rico
Bayamon, Puerto Rico
Recruiting
Puerto Rico
Ponce, Puerto Rico
Recruiting
Puerto Rico
San Juan, Puerto Rico
Not yet recruiting
Russian Federation
Ekaterinburg, Russian Federation
Withdrawn
Russian Federation
Krasnodar, Russian Federation
Not yet recruiting
Russian Federation
Moscow, Russian Federation
Withdrawn
Russian Federation
Moscow, Russian Federation
Not yet recruiting
Russian Federation
Nizny Novgorod, Russian Federation
Not yet recruiting
Russian Federation
Novosibirsk, Russian Federation
Withdrawn
Russian Federation
Obninsk, Russian Federation
Withdrawn
Russian Federation
Petrozavodsk, Russian Federation
Not yet recruiting
Russian Federation
Pyatigorsk, Russian Federation
Not yet recruiting
Russian Federation
Rostov-Na-Donu, Russian Federation
Not yet recruiting
Russian Federation
Sochi, Russian Federation
Withdrawn
Russian Federation
St. Petersburg, Russian Federation
Not yet recruiting
Russian Federation
Syktyvkar, Russian Federation
Not yet recruiting
Russian Federation
Tomsk, Russian Federation
Withdrawn
Russian Federation
Velikiy Novgorod, Russian Federation
Not yet recruiting
Russian Federation
Volgograd, Russian Federation
Not yet recruiting
Spain
Barcelona, Spain
Not yet recruiting
Spain
Madrid, Spain
Not yet recruiting
Spain
Madrid, Spain
Recruiting
Spain
Málaga, Spain
Withdrawn
Spain
Salamanca, Spain
Not yet recruiting
Sweden
Göteborg, Sweden
Recruiting
Sweden
Linköping, Sweden
Recruiting
Sweden
Luleå, Sweden
Recruiting
Sweden
Lund, Sweden
Withdrawn
Sweden
Uppsala, Sweden
Recruiting
Turkey
Ankara, Turkey
Not yet recruiting
Turkey
Ankara, Turkey
Recruiting
Turkey
Bursa, Turkey
Not yet recruiting
Turkey
Istanbul, Turkey
Not yet recruiting
Turkey
Istanbul, Turkey
Withdrawn
Turkey
Izmir, Turkey
Not yet recruiting
Turkey
Izmir, Turkey
Withdrawn
Turkey
Kayseri, Turkey
Not yet recruiting
United Kingdom
Glasgow, United Kingdom
Not yet recruiting
United Kingdom
London, United Kingdom
Not yet recruiting
United Kingdom
London, United Kingdom
Withdrawn
United Kingdom
Newcastle Upon Tyne, United Kingdom
Not yet recruiting
United Kingdom
Plymouth, United Kingdom
Not yet recruiting
United Kingdom
Portsmouth, United Kingdom
Not yet recruiting
United Kingdom
Southampton, United Kingdom
Withdrawn
United Kingdom
Sutton, United Kingdom
Not yet recruiting
United Kingdom
Swansea, United Kingdom
Not yet recruiting