E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell Lymphoma refractory |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
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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 |
To evaluate the overall response rate (Complete Remission + Partial Remission) of YM155 per the International Working Group Criteria (IWG, 2007) during 15 cycles of treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy, safety and tolerability of YM155 during 15 cycles of treatment. |
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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 |
QT sub-study: included in the main study protocol. The objective of the sub-study is to assess the potential effect of YM155 on cardiac intervals including QT.
Pharmacogenomic sub-study: included in the main study protocol. The objective of this research is to comprehensively analyze: • Suspected disease-related genes • Genes potentially involved in drug excretion and/or metabolism • Genes of relevance to toxicity/safety issues, to be identified in a precautionary / retrospective setting.
Biomarker sub-study: included in the main study protocol. The objective of this research is to comprehensively analyze protein expression that may yield prognostic, predictive or mechanistic information. |
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E.3 | Principal inclusion criteria |
- Male or female subjects aged 18 years or older. - Histologically confirmed primary Diffuse Large B-Cell Lymphoma (DLBCL) of any stage. - Refractory to the last treatment regimen, defined as one of the following: o The subject failed to obtain at least a Partial Response (PR) at anytime while receiving the last treatment regimen. o The subject obtained at least a PR during the last treatment regimen, but later progressed while still on the treatment regimen. o The subject obtained at least a PR to the last treatment regimen, but progressed within 6 months following completion of the last treatment regimen. - Subjects must have been previously treated with the following treatment regimens: o Anthracycline-based combination chemotherapy with rituximab o Second-line combination chemotherapy o Autologous bone marrow transplant (BMT) or autologous peripheral blood stem cell transplant (PBSCT) if eligible and did not refuse. Subjects that were not eligible for an autologous BMT or PBSCT or subjects that were eligible and refused the procedure are candidates for this trial. - At least one measurable lesion defined as > or equal to 1.5 cm in the longest transverse diameter by CT scan - No known central nervous system (CNS) involvement - Eastern Cooperative Oncology Group (ECOG) performance status < or equal to 2 |
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E.4 | Principal exclusion criteria |
- Transformed, discordant or composite lymphoma. - Any therapy for lymphoma within 21 days prior to the first YM155 dose. - Within 4 weeks of the baseline FDG-PET scan, subjects cannot have had the following: o Radiation therapy. o Surgical procedures (except biopsies and central catheter / port placement). o Active infection (bloodstream or deep tissue). - Inadequate marrow, hepatic and/or renal function at the Baseline Visit defined as: o Serum creatinine superior or equal to 1.5 x Upper Limit of Normal (ULN) or calculated serum creatinine clearance < 60 mL/min. o Absolute Neutrophil Count (ANC) inferior or equal to 750/mm3. o Platelet inferior or equal to 50,000/mm3. o Alanine Transaminase (ALT) and Aspartate Transaminase (AST) superior or equal to 2.5 x ULN; superior or equal to 5 x ULN if secondary to liver metastases. - Subjects received > 3 prior treatment regimens for their lymphoma. The following should be considered when determining the number of prior treatment regimens: o Any planned maintenance therapy should be considered as part of the previous treatment regimen o Any preparative treatment (salvage chemotherapy, high-dose chemotherapy, radiation therapy, etc.) should be included with the autologous BMT or autologous PBSCT as one treatment regimen. - Allogeneic BMT or allogeneic PBSCT. - History of other malignancy requiring treatment within 2 years prior to the first dose of YM155, except for treated basal or squamous cell carcinoma of the skin or in situ cervical cancer |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (Complete Remission + Partial Remission) per the International Working Group Criteria (IWG, 2007) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 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 | 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 | Information not present in EudraCT |
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 |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |