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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Janssen Research & Development, LLC
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01855750
First received: May 14, 2013
Last updated: August 7, 2014
Last verified: August 2014

May 14, 2013
August 7, 2014
September 2013
June 2018   (final data collection date for primary outcome measure)
Event-free survival [ Time Frame: Up to disease progression, relapse from complete response, initiation of subsequent systemic antilymphoma therapy after completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first, up to Year 7 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01855750 on ClinicalTrials.gov Archive Site
  • Progression-free survival [ Time Frame: Up to disease progression, relapse from complete response, or death, whichever occurs first, up to Year 7 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to the date of the participants death, up to Year 7 ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: Up to completion of chemotherapy treatment, up to Year 7 ] [ Designated as safety issue: No ]
  • Time to worsening symptoms in the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [ Time Frame: Up to the start date of the worsening of patient symptoms, up to Year 7 ] [ Designated as safety issue: No ]
  • Oral plasma clearance of ibrutinib [ Time Frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 ] [ Designated as safety issue: No ]
  • Oral volume of distribution at steady state of ibrutinib [ Time Frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve of ibrutinib [ Time Frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 ] [ Designated as safety issue: No ]
  • Minimum observed plasma concentration of ibrutinib [ Time Frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2 ] [ Designated as safety issue: No ]
  • Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
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
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

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).

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. The study will include screening, active treatment, and posttreatment follow-up phases. The study will end when 50% of participants have died or the sponsor terminates the study, whichever occurs first (up to approximately 7 years). 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Lymphoma
  • Drug: Ibrutinib
    560 mg capsules administered by mouth once daily (21-day cycles)
  • Drug: Placebo
    4 matched capsules administered by mouth once daily (21-day cycles)
  • Drug: Rituximab
    375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
  • Drug: Cyclophosphamide
    750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
  • Drug: Doxorubicin
    50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
  • Drug: Vincristine
    1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
  • Drug: Prednisone (or equivalent)
    100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
  • Placebo Comparator: Treatment Arm A: placebo + R-CHOP
    Treatment Arm A = placebo + R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
    Interventions:
    • Drug: Placebo
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone (or equivalent)
  • Experimental: Treatment Arm B: ibrutinib + R-CHOP
    Treatment Arm B = ibrutinib + R-CHOP
    Interventions:
    • Drug: Ibrutinib
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone (or equivalent)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
800
June 2020
June 2018   (final data collection date for primary outcome measure)

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 within 14 days 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
Both
18 Years and older
No
Contact: 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
United States,   Argentina,   Australia,   Belgium,   Brazil,   Canada,   China,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United Kingdom
 
NCT01855750
CR102118, PCI-32765DBL3001, U1111-1139-6222, 2013-000959-40
Yes
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Pharmacyclics
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP