E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PREVIOUSLY UNTREATED PATIENTS WITH CD20-POSITIVE DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) |
|
E.1.1.1 | Medical condition in easily understood language |
CD20-Positive Diffuse Large B-Cell Lymphoma |
|
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 | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10012819 |
E.1.2 | Term | Diffuse large B-cell lymphomas |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 this study is to demonstrate superiority in PFS with G-CHOP
compared with rituximab plus chemotherapy (R-CHOP) in previously untreated patients
with CD20-positive DLBCL, based on investigator-assessed PFS. |
|
E.2.2 | Secondary objectives of the trial |
OS up to approximately 78 months
ORR at the end of treatment, assessed by the investigator and the IRC 24 weeks
CR rate at the end of treatment, assessed by investigator and IRC 24 weeks
EFS, defined as time to progression or relapse, or initiation of nonprotocol- specified anti-lymphoma therapy, or death, whichever occurs first up to approximately 78 months
PFS assessed by the Independent Review Committee up to Event-free survival, defined as time to progression or relapse, or initiation of nonprotocol- specified anti-lymphoma therapy, or death, whichever occurs first
Disease-free survival, assessed by investigator up to approximately 78 months
Duration of response, assessed by the investigator up to approximately 78 months
Time to next lymphoma treatment up to approximately 78 months
Incidence of adverse events up to approximately 78 months
Quality of life up to approximately 78 months
Medical resource utilization up to approximately 78 months |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients, >/= 18 years of age
Previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL)
At least 1 bi-dimensionally measurable lesion (>1.5 cm in is largest dimension on the CT scan)
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Adequate hematological function
|
|
E.4 | Principal exclusion criteria |
History of severe allergic or anaphylactic reactions to humanized or
murine monoclonal antibodies or known sensitivity or allergy to murine
products or any component of CHOP or GA101
Contraindication to any of the individual components of CHOP, including
prior receipt of anthracyclines
Diagnosis of transformed lymphoma (follicular IIIB) if previously treated
with radiotherapy, chemotherapy, or immunotherapy
Prior therapy for DLBCL, with the exception of nodal biopsy or local
irradiation
Prior treatment with cytotoxic drugs or rituximab for another condition
(e.g., rheumatoid arthritis) or prior use of an anti-CD20 antibody
Prior use of any monoclonal antibody within 3 months of the start of
Cycle 1
Ongoing corticosteroid use of > 30 mg/day of prednisone or equivalent,
for purposes other then lymphoma symptom control
Primary CNS lymphoma and secondary CNS invilvement by lymphoma,
MCL, or histologic evidence of transformation to a Burkitt lymphoma,
primary mediastinal DLBCL, primary effusion lymphoma, plasmablastic
lymphoma, and primary cutaneous DLBCL
Patients with a history of confirmed PML |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is PFS, as determined by the investigator,
defined as the time from the date of randomization until the first
occurrence of disease progression, relapse, or death from any cause.
While the primary efficacy endpoint is investigator-assessed PFS, PFS
based on IRC assessments will also be analyzed to support the primary
analysis. In the United States, IRC-assessed PFS will be the basis for
regulatory decisions. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to approximately 78 months |
|
E.5.2 | Secondary end point(s) |
- ORR at the end of treatment, assessed by the investigator and IRC
- CR rate at the end of treatment, assessed by investigator and IRC
- PFS assessed by the IRC
- Event-free survival, defined as time to progression or relapse, or initiation of non-protocol-specified anti-lymphoma therapy, or death, whichever occurs first
- Disease-free survival, assessed by investigator
- Duration of response, assessed by the investigator
- Time to next lymphoma treatment
- Incidence of adverse events
- Quality of life
- Medical resource utilization |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 months for PFS, OS, ORR, CRR
up to approximately 78 months for all other measures |
|
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 | No |
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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 87 |
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 |
Canada |
China |
Denmark |
Italy |
Japan |
Austria |
Slovakia |
Australia |
Brazil |
Czech Republic |
Germany |
Hungary |
India |
Korea, Democratic People's Republic of |
Spain |
Mexico |
Poland |
Russian Federation |
Switzerland |
Taiwan |
United Kingdom |
United States |
|
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
|
The end of the study is defined as the last patient’s last visit and will occur approximately 6.5 years (78 months) after the first patient is enrolled to allow all patients to have a minimum of 3 years of follow-up post-treatment |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |