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 | 18.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 the study is to evaluate the ORR of ibrutinib, as assessed by the Independent Review Committee (IRC), in subjects with chemoimmunotherapy-resistant FL |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to:
Evaluate the duration of response
Evaluate the safety of ibrutinib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Histologic proof of Grade 1, 2, or 3a follicular lymphoma (FL) without clinical or pathological evidence of transformation
•Previously treated with at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen; last prior line of therapy includes an anti CD20 monoclonal antibody-containing chemotherapy regimen (separate lines of therapy are defined as different regimens that are either separated by disease progression, refractory disease, or relapsed disease)
•Resistant disease to the last therapy, defined as progression of disease during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen
•At least 1 measurable site of disease according to International Working Group Revised Response Criteria for Malignant Lymphoma
•Eastern Cooperative Oncology Group performance status grade 0 or 1
•Hematology and biochemical laboratory values must be within protocol-defined parameters within 7 days prior to enrollment
•Agrees to protocol-defined use of effective contraception
•Women of childbearing potential must have a negative serum or urine pregnancy test at screening
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E.4 | Principal exclusion criteria |
•Prior nitrosoureas within 6 weeks, chemotherapy within 3 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 first dose of study drug
•Prior treatment with PCI-32765 or other Bruton's tyrosine kinase
inhibitors (patients who progressed or became refractory while on
treatment with P13K inhibitors are excluded)
•Concurrent enrollment in another therapeutic investigational clinical treatment study
•Received a prior allogeneic hematopoietic stem cell transplant (prior autologous hematopoietic stem cell transplant is allowed)
•Known central nervous system lymphoma
•History of prior malignancy (except malignancy treated with curative intent and with no known active disease present for >=3 years before enrollment, 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 enrollment
•Requires anticoagulation with warfarin or equivalent vitamin K antagonists
•Requires treatment with strong cytochrome P450 (CYP)3A4/5 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 (HIV) or active infection with Hepatitis C or active infection with Hepatitis B or any uncontrolled active systemic infection requiring intravenous antibiotics
•Women who are pregnant or breastfeeding
•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 PCI-32765 capsules, or put the study outcomes at undue risk
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 2 years after the last patient is enrolled |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time frame = every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 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 | 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 |
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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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
Belgium |
France |
Germany |
Italy |
Poland |
Russian Federation |
Spain |
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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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 | 43 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 43 |