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. Objective: assessment of potential QT prolongation by YM155 during Cycle 1 only. |
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E.3 | Principal inclusion criteria |
- Male or female subjects aged 18 years or older. - Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) (including transformed 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 Remission (PR) at anytime while receiving the previous treatment regimen. o The subject obtained at least a PR during the previous treatment regimen, but later progressed while still on the treatment regimen. o The subject obtained at least a PR to the previous treatment regimen, but progressed within 6 months following completion of the previous treatment regimen. - Subjects who have not received an autologous Bone Marrow Tansplant (BMT) or autologous Peripheral Blood Stem Cell Transplant (PBSCT) must have refused or been ineligible for that procedure. - At least one measurable lesion defined as superior or equal to 1.5 cm in the longest transverse diameter by CT scan. - No known central nervous system involvement. - Eastern Cooperative Oncology Group (ECOG) performance status inferior or equal to 2. |
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E.4 | Principal exclusion criteria |
- 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. Subjects are permitted to have had an autologous BMT or autologous PBSCT as one of the prior treatment regimens. If a subject has had an autologous BMT or autologous PBSCT, it, along with any preparative treatment (salvage chemotherapy, high-dose chemotherapy, radiation therapy, etc.) is included as one treatment regimen. - Allogeneic BMT or allogeneic PBSCT. - History of other malignancy requiring treatment within 5 years, 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
| 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 | 5 |
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
| |
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 |