E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Indolent Non-Hodgkin Lymphoma (iNHL) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10029621 |
E.1.2 | Term | Non-Hodgkin's lymphomas unspecified histology indolent |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate whether the addition of ibrutinib to bendamustine and rituximab (BR) combination or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination will result in prolongation of PFS compared with either BR or R-CHOP alone in subjects with previously treated iNHL (FL or MZL). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare treatment groups in terms of the following: overall survival (OS) complete response rate (CR) overall response rate ORR (CR+PR) duration of response (DOR) patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) safety of ibrutinib when combined with BR or R-CHOP |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 regarding 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 7 years after the first participant is randomized |
|
E.5.2 | Secondary end point(s) |
Overall survival 1/ Overall survival 2/ Complete response rate 3/ Overall response rate 4/ Duration of response 5/ 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) 6/ Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ Up to approximately 7 years after the first participant is randomized 2/ Up to approximately 7 years after the first participant is randomized 3/ Up to approximately 7 years after the first participant is randomized 4/ Up to approximately 7 years after the first participant is randomized 5/ Up to approximately 7 years after the first participant is randomized 6/ Up to 30 days after the last dose of study medication |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 68 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
China |
Israel |
Japan |
Korea, Republic of |
United States |
France |
Poland |
Sweden |
Spain |
Germany |
Italy |
Belgium |
Russian Federation |
Turkey |
Ukraine |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Per protocol, the end of the trial is defined as the time when 50% of subjects have died. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |