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
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| ClinicalTrials.gov Identifier: NCT01974440 |
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Recruitment Status :
Active, not recruiting
First Posted : November 1, 2013
Last Update Posted : April 30, 2021
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Sponsor:
Janssen Research & Development, LLC
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma | Drug: Bendamustine Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: PCI-32765 (Ibrutinib) Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 403 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | January 31, 2014 |
| Estimated Primary Completion Date : | February 28, 2022 |
| Estimated Study Completion Date : | February 28, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Cyclophosphamide
Prednisone
Vincristine sulfate
Bendamustine hydrochloride
Bendamustine
Doxorubicin
Rituximab
Ibrutinib
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Bendamustine
90 milligram per meter square (mg/m^2) administered intravenously on Days 1 to 2 of Cycles 1 to 6. Drug: Rituximab 375 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Cyclophosphamide 750 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Doxorubicin 50 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Vincristine 1.4 mg/m^2 (maximum total 2 mg) administered intravenously on Day 1 of Cycles 1 to 6. Drug: Prednisone 100 mg administered orally on Days 1 to 5 of Cycles 1 to 6. Drug: Placebo Placebo (4 capsules) matched to ibrutinib administered orally once daily, continuously starting on Cycle 1, Day 1. |
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Experimental: Treatment Arm B
Treatment Arm B = background immune-chemotherapy (BR or R-CHOP) for 6 cycles + PCI-32765 (Ibrutinib).
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Drug: Bendamustine
90 milligram per meter square (mg/m^2) administered intravenously on Days 1 to 2 of Cycles 1 to 6. Drug: Rituximab 375 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Cyclophosphamide 750 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Doxorubicin 50 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6. Drug: Vincristine 1.4 mg/m^2 (maximum total 2 mg) administered intravenously on Day 1 of Cycles 1 to 6. Drug: Prednisone 100 mg administered orally on Days 1 to 5 of Cycles 1 to 6. Drug: PCI-32765 (Ibrutinib) 560 mg (4*140 mg) capsules administered orally once daily, continuously starting on Cycle 1, Day 1. |
Primary Outcome Measures :
- Progression-free survival [ Time Frame: Up to approximately 7 years after the first participant is randomized ]
Secondary Outcome Measures :
- Overall survival [ Time Frame: Up to approximately 7 years after the first participant is randomized ]
- Complete response rate [ Time Frame: Up to approximately 7 years after the first participant is randomized ]
- Overall response rate [ Time Frame: Up to approximately 7 years after the first participant is randomized ]
- Duration of response [ Time Frame: Up to approximately 7 years after the first participant is randomized ]
- 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 ]
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01974440
Locations
Show 135 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Pharmacyclics LLC.
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT01974440 |
| Other Study ID Numbers: |
CR102786 PCI-32765FLR3001 ( Other Identifier: Janssen Research & Development, LLC ) 2013-003093-27 ( EudraCT Number ) |
| First Posted: | November 1, 2013 Key Record Dates |
| Last Update Posted: | April 30, 2021 |
| Last Verified: | April 2021 |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Janssen Research & Development, LLC:
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Lymphoma Follicular lymphoma Marginal zone lymphoma Indolent Non-Hodgkin lymphoma PCI-32765 Ibrutinib Bendamustine |
Rituximab Cyclophosphamide Doxorubicin Vincristine Prednisone R-CHOP |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Bendamustine Hydrochloride Rituximab Doxorubicin Vincristine Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents Glucocorticoids |