Clinical trial NCT01974440: A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Participants With Previously Treated Indolent Non-Hodgkin Lymphoma
Official title: A 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: Lymphoma
Follicular lymphoma
Marginal zone lymphoma
Indolent Non-Hodgkin lymphoma
PCI-32765
Ibrutinib
Bendamustine
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone
R-CHOP
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Pharmacyclics LLC.
First posted: 2013-11-01
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 participants 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 participants with follicular lymphoma or marginal zone lymphoma. The study will include the following phases: Screening, Treatment, and a Post-treatment Follow-up. Eligible participants 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 milligram \[mg\] 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, whichever comes first. 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.

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 initial diagnosis and without evidence of pathological transformation or clinical signs suggesting transformation
* At least 1 prior treatment with a CD20 antibody combination chemo-immunotherapy regimen
* Disease that has relapsed or was refractory after prior chemo-immunotherapy
* 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
* Requires treatment with strong CYP3A inhibitors
* Clinically significant cardiovascular disease
* Known history of human immunodeficiency virus or active hepatitis C virus (HCV; ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]-positive) or active hepatitis B virus (HBV; DNA PCR-positive) infection 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

Primary outcomes:
measure: Primary Analysis: Progression Free Survival (PFS): Stratified Analysis
timeFrame: Up to 8 years
measure: Supplementary Analysis: Progression Free Survival: Unstratified Analysis - Participants With Marginal Zone Lymphoma (MZL)
timeFrame: Up to 8 years
Secondary outcomes:
measure: Primary Analysis: Overall Survival (OS): Stratified Analysis
timeFrame: Up to 8 years
measure: Supplementary Analysis: Overall Survival: Unstratified Analysis - Participants With MZL
timeFrame: Up to 8 years
measure: Primary Analysis: Complete Response Rate (CRR): Stratified Analysis
timeFrame: Up to 8 years
measure: Supplementary Analysis: Complete Response Rate: Unstratified Analysis - Participants With MZL
timeFrame: Up to 8 years
measure: Primary Analysis: Overall Response Rate (ORR): Stratified Analysis
timeFrame: Up to 8 years
measure: Supplementary Analysis: Overall Response Rate: Unstratified Analysis - Participants With MZL
timeFrame: Up to 8 years
measure: Primary Analysis: Duration of Response (DOR): Stratified Analysis
timeFrame: Up to 8 years
measure: Supplementary Analysis: Duration of Response: Unstratified Analysis - Participants With MZL
timeFrame: Up to 8 years
measure: Primary Analysis: Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) Questionnaire
timeFrame: Up to 8 years
measure: Supplementary Analysis: Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) Questionnaire: Participants With MZL
timeFrame: Up to 8 years
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Placebo + Chemoimmunotherapy (CIT) arm: From Day 1 up to 30 days after date of last dose of study medication (up to 8 years); Ibrutinib + CIT arm: From Day 1 up to 30 days after date of last dose of study medication (up to 8 years 8 months)
measure: Number of Participants With TEAEs: Participants With MZL
timeFrame: Placebo + Chemoimmunotherapy (CIT) arm: From Day 1 up to 30 days after date of last dose of study medication (up to 8 years); Ibrutinib + CIT arm: From Day 1 up to 30 days after date of last dose of study medication (up to 8 years 8 months)
Other outcomes:
Locations:
city: Gilbert
country: United States
state: Arizona
city: Campbell
country: United States
state: California
city: Duarte
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Ocala
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Westwood
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Lafayette
country: United States
state: Louisiana
city: Scarborough
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Battle Creek
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Saint Louis Park
country: United States
state: Minnesota
city: Denville
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Pinehurst
country: United States
state: North Carolina
city: Bend
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Sioux Falls
country: United States
state: South Dakota
city: Houston
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Spokane
country: United States
state: Washington
city: Green Bay
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Ciudad Autonoma Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Capital
country: Argentina
city: Mendoza
country: Argentina
city: Santa Fe
country: Argentina
city: Adelaide
country: Australia
city: Fitzroy
country: Australia
city: Heidelberg
country: Australia
city: South Brisbane
country: Australia
city: Wahroonga
country: Australia
city: Westmead
country: Australia
city: Anderlecht
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Namur
country: Belgium
city: Wilrijk
country: Belgium
city: Porto Alegre
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Beijing
country: China
city: Chengdu
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Harbin
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Nice Cedex 2
country: France
city: Paris
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Berlin
country: Germany
city: Gießen
country: Germany
city: Göttingen
country: Germany
city: Ludwigshafen
country: Germany
city: Magdeburg
country: Germany
city: Mainz
country: Germany
city: Munchen
country: Germany
city: Wiesbaden
country: Germany
city: Hadera
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Nahariya
country: Israel
city: Netanya
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Chuo Ku
country: Japan
city: Hiroshima shi
country: Japan
city: Isehara
country: Japan
city: Kobe
country: Japan
city: Nagoya-shi
country: Japan
city: Osaka Sayama shi
country: Japan
city: Sapporo-shi
country: Japan
city: Sendai shi
country: Japan
city: Suita-shi
country: Japan
city: Tokyo
country: Japan
city: Jeollanam-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Gdynia
country: Poland
city: Olsztyn
country: Poland
city: Warszawa
country: Poland
city: Bayamon
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Krasnodar
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizny Novgorod
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Rostov-On-Don
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Pozuelo de Alarcon
country: Spain
city: Salamanca
country: Spain
city: Göteborg
country: Sweden
city: Linköping
country: Sweden
city: Luleå
country: Sweden
city: Uppsala
country: Sweden
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
city: Cherkasy
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Khmelnitskiy
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Portsmouth
country: United Kingdom
city: Sutton
country: United Kingdom
city: Swansea
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: