E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL) |
|
E.1.1.1 | Medical condition in easily understood language |
Central Nervous System Cancer and Testicular Cancer |
|
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 | 10036685 |
E.1.2 | Term | Primary central nervous system lymphoma |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10043302 |
E.1.2 | Term | Testicular cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
To assess the clinical benefit of nivolumab in subjects with relapsed/refractory PCNSL or relapsed/refractory PTL as measured by ORR by blinded Independent Central Review (BICR). |
|
E.2.2 | Secondary objectives of the trial |
-) To assess PFS based on BICR assessment for PCNSL or PTL, respectively
-) To assess ORR and DOR based on investigator assessment for PCNSL or PTL, respectively
-) To assess overall survival (OS) for PCNSL or PTL, respectively |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
This protocol will include both sample collection and residual sample storage for additional research. This collection for additional research is intended to expand the translational research and development capability at BMS, and will support as yet undefined research aims that will advance our understanding of disease and options for treatment. It may also be used to support health authority requests for analysis, and advancement of pharmacodiagnostic development to better target drugs to the right patients. |
|
E.3 | Principal inclusion criteria |
1a) Men and women, age of more than 18 years old at the time of screening
b) Subjects with pathologically confirmed PCNSL or PTL who progressed after or did not respond to at least 1 line of systemic therapy (PCNSL prior therapy may include: high-dose methotrexate [HD-MTX], HD-MTX based regimen, high dose cytarabine, radiation therapy alone as treatment or as part of consolidation therapy, high dose therapy with autologous stem cell transplant as part of consolidation therapy, and/or intraocular MTX alone or as part of consolidation therapy; PTL prior therapy may include: chemoimmunotherapy such as CHOP-R or any other regimens, with/without prophylactic radiation to contralateral testis or orchiectomy or intrathecal chemotherapy)
c) Radiologically measurable disease within 28 days of first dose
d) Karnofsky performance status of 70 or higher |
|
E.4 | Principal exclusion criteria |
a) Intraocular PCNSL without evidence of brain disease. Patients with prior history of intraocular
involvement treated only with intraocular methotrexate and no prior systemic therapy are excluded.
b) PCNSL with systemic disease
c) PCNSL patients who cannot undergo magnetic resonance imaging assessments
d) Patients with brain stem lesions
e) Active, known, or suspected autoimmune disease
f) Known history of positive test for human immunodeficiency virus or known acquired immunodeficiency
syndrome
g) Prior treatment with an anti-programmed death ligand (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is BICR-assessed ORR. It is defined as the best response designation recorded between the date
of first study drug dose and the date of initial objectively documented progression per criteria or the date of subsequent therapy, whichever occurs first.
The BICR-assessed objective response will be further characterized by the DOR. DOR is defined as the time from first response (partial response [PR] or complete response [CR]) to the date of initial objectively documented progression as determined using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria for PCNSL and Lugano 2014 response evaluation for PTL, as determined by BICR, or death due to any cause, whichever occurs first. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be analyzed 6 months after last patient first treatment in each cohort. All treated subjects will be evaluated. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are PFS based on BICR assessment, ORR and DOR based on investigator assessment, and OS. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments for PCNSL will occur every 2 months for 2 years, then every 6 months until disease progression.
Tumor assessments for PTL will occur every 2 months for 6 months, then every 3 months for 1.5 years, then every 6 months until disease progression. |
|
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 | Yes |
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 | No |
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) | 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 | 30 |
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 |
Czech Republic |
France |
Hong Kong |
Hungary |
Israel |
Italy |
Russian Federation |
Singapore |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 22 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 1 |