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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061275 |
E.1.2 | Term | Mantle cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of the study is to evaluate the overall response rate of ibrutinib, as assessed by the Independent Review Committee (IRC), in subjects with MCL who received at least 1 prior rituximab-containing chemotherapy regimen and who progressed after bortezomib therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
•To evaluate the duration of response
•To evaluate progression-free survival (PFS)
•To evaluate overall survival
•To evaluate the safety of ibrutinib
•To characterize the pharmacokinetics of ibrutinib after oral dosing
•To explore the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information
•To evaluate patient-reported outcomes (PROs) utilizing the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EuroQol (EQ-5D)
•To identify biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways and to explore their association with response to ibrutinib
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of confirmed mantle cell lymphoma (MCL) with at least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma.
- Must have received at least 1prior rituximab-containing chemotherapy regimen, but no more than 5 prior regimens.
- Must have received at least 2 cycles of bortezomib therapy (single-agent or in combination) and have documented progressive
disease during or after bortezomib therapy
- Eastern Cooperative Oncology Group performance status score 0, 1, or 2.
- Hematology and biochemical values within protocol-defined parameters. |
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E.4 | Principal exclusion criteria |
- Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other
investigational agents within 3 weeks, or major surgery within 4 weeks of the first dose of study drug
- Prior treatment with ibrutinib or other Bruton’s tyrosine kinase inhibitors.
- More than 5 prior lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a >6 month treatment-free interval.
- Known central nervous system lymphoma.
- Diagnosed or treated for malignancy other than MCL, except malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of study drug and felt to be at low risk for recurrence by the treating physician, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, or adequately treated cervical carcinoma in situ without evidence of disease.
- History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists. - Requires treatment with strong CYP3A4/5 inhibitors.
- 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 infection with hepatitis C virus or hepatitis B virus or any
uncontrolled active systemic infection.
- 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the overall response rate
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year after the last patient is enrolled |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are
1/ Overall survival rate
2/ Progression-free survival rate
3/ Mean change from baseline in the Lym subscale
4/ Mean change from baseline in the EQ-5D-5L
index
5/ Mean plasma concentrations of ibrutinib
6/ Maximum observed plasma concentration of
ibrutinib
7/ Minimum observed plasma concentration of
ibrutinib
8/ Area under the plasma concentration-time curve
from time 0 to 24 hours of ibrutinib
9/ The number of participants affected by an adverse event
10/ Overall response rate |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ 1 year after the last patient is enrolled and 2
years after the last patient is enrolled
2/ 1 year after the last patient is enrolled and 2
years after the last patient is enrolled
3/ 1 year after the last patient is enrolled and 2
years after the last patient is enrolled
4/ 1 year after the last patient is enrolled and 2
years after the last patient is enrolled
5/ Up to Cycle 2, Day 21
6/ Up to Cycle 2, Day 21
7/ Up to Cycle 2, Day 21
8/ Up to Cycle 2, Day 21
9/ Up to 30 days after the last dose of study medication
10/ 1 year after the last patient is enrolled and 2
years after the last patient is enrolled |
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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 | 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 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Belgium |
France |
Italy |
Spain |
Israel |
Poland |
Russian Federation |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The primary analysis (primary end point is ORR) will be conducted 1 year after last patient has been enrolled, long term follow-up until 2 years after last patient has been enrolled at which point the study will end.
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |