E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10029473 |
E.1.2 | Term | Nodular (follicular) lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Analysis Study 1
To evaluate whether the addition of ibrutinib to rituximab will result in prolongation of progression-free survival (PFS) when compared with rituximab alone in treatment naïve subjects with follicular lymphoma
Discontinuation Analysis Study
For subjects who are re-randomized for Part 2, to evaluate whether continuous treatment with ibrutinib will result in prolongation of PFS when compared with finite treatment with ibrutinib |
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E.2.2 | Secondary objectives of the trial |
Analysis Study 1
* During Part 1, to evaluate whether the addition of ibrutinib to rituximab will result in improvement in investigator-assessed CR rate and ORR when compared with rituximab alone in treatment naïve subjects with follicular lymphoma
* To evaluate whether the addition of ibrutinib to rituximab will result in
a reduction in infusion-related reactions
* To evaluate whether the addition of ibrutinib to rituximab will result in prolongation of OS (Arm A vs. Arm B) through Part 2
* To evaluate the safety and tolerability of ibrutinib combined with rituximab compared to rituximab alone in treatment naïve subjects with follicular lymphoma
Discontinuation Analysis Study
* To evaluate the long-term safety and tolerability of ibrutinib after completing the rituximab maintenance in treatment naïve subjects with follicular lymphoma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Histologically confirmed diagnosis of follicular lymphoma CD20+
(Grade 1, 2 or 3a) Ann Arbor Stage II, III or IV disease.
* Measurable disease
* Subjects 70 years of age or older; OR subjects 60-69 years of age who
have one or more comorbidities.
* Meets one or more Groupe d'Etude des Lymphomes Folliculaire (GELF)
criteria.
* Adequate hematologic function within protocol-defined parameters.
* Adequate hepatic and renal function within protocol-defined
parameters.
* ECOG performance status score of 0-2.
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E.4 | Principal exclusion criteria |
* Transformed lymphoma
* Prior treatment for follicular lymphoma
* Central nervous system lymphoma or leptomeningeal disease
* Currently active, clinically significant cardiovascular disease
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E.5 End points |
E.5.1 | Primary end point(s) |
Analysis Study 1:
Progression-free survival (PFS) in Part 1
Discontinuation Analysis Study:
Progression-free survival (PFS) in Part 2 (Arm A1 vs. Arm A2) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis Study 1:
Approx. 5 years after the start of the study
Discontinuation Analysis Study:
Approx. 3 years when all the re-randomized subjects have been followed for approximately 36 months |
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E.5.2 | Secondary end point(s) |
Analysis Study 1:
* Complete response (CR) rate in Part 1 as defined by the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma (Cheson 2014)
* Overall response rate (ORR) (Cheson 2014) in Part 1
* Infusion-related reaction rate (Arm A vs Arm B)
* Overall survival (OS) (Arm A vs. Arm B) through Part 2
* Frequency, severity, seriousness, and relatedness of adverse events (AEs) in Part 1
Discontinuation Analysis Study:
Frequency, severity, seriousness, and relatedness of adverse events (AEs) in Part 2 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
CR and ORR:
Approx. 5 years after the start of the study
OS:
Approx. 8 years [(5 years (Part 1) + 3 years (Part 2)]
Analysis Study 1:
Frequency, severity , seriousness and relatedness of AE in Part 1 will take approx. 5 years
Discontinuation Analysis Study:
Frequency, severity, seriousness, and relatedness of adverse events in Part 2 will take approx. 3 years after Part 1 is complete |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 115 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Greece |
Hungary |
Israel |
Italy |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |