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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01974440
First received: October 28, 2013
Last updated: June 17, 2016
Last verified: June 2016
  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 participants with previously treated indolent Non-Hodgkin lymphoma.

Condition Intervention Phase
Lymphoma
Drug: Bendamustine
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: PCI-32765 (Ibrutinib)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to approximately 7 years after the first participant is randomized ] [ Designated as safety issue: No ]

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 ]

Enrollment: 403
Study Start Date: January 2014
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Experimental: Treatment Arm B
Treatment Arm B = background immune-chemotherapy (BR or R-CHOP) for 6 cycles + PCI-32765 (Ibrutinib).
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.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01974440

  Show 133 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Pharmacyclics
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01974440     History of Changes
Other Study ID Numbers: CR102786  PCI-32765FLR3001  2013-003093-27 
Study First Received: October 28, 2013
Last Updated: June 17, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: National Health and Medical Research Council
China: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Russia: Pharmacological Committee, Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Ethics Commission
Spain: Spanish Agency of Medicines
Australia: Department of Health and Ageing Therapeutic Goods Administration
Great Britain: Medicines and Healthcare Products Regulatory Agency
Great Britain: Research Ethics Committee

Keywords provided by Janssen Research & Development, LLC:
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:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Bendamustine Hydrochloride
Liposomal doxorubicin
Doxorubicin
Prednisone
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
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids

ClinicalTrials.gov processed this record on August 23, 2016