E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell lymphoma. |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse large B-cell lymphoma. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012857 |
E.1.2 | Term | Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective is to evaluate if progression-free survival with pola-R-mini-CHP is superior to that of R-mini-CHOP. |
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E.2.2 | Secondary objectives of the trial |
To compare response duration, complete remission rate (CR), overall response rate (ORR), health-related quality of life (HRQOL), lymphoma specific survival (LSS), overall survival (OS), and safety between these regimens. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥80 years or frail ≥75 years, according to simplified comprehensive geriatric assessment
2. Histologically confirmed lymphoma belonging to one of the following subtypes: a. diffuse large B-cell lymphoma, including transformation from an indolent lymphoma b. follicular lymphoma grade 3B c. T-cell/histiocyte-rich LBCL d. primary cutaneous DLBCL, leg type e. EBV-positive DLBCL, NOS f. primary mediastinal LBCL g. high grade B-cell lymphoma with MYC/BCL2 rearrangement
3. Stage II-IV disease
4. At least 1 measurable site of disease (>1.5 cm long axis)
5. No previous treatment for lymphoma
6. WHO performance status 0 – 3 (Grade 3 if related to DLBCL)
7. Written informed consent |
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E.4 | Principal exclusion criteria |
1. Severe cardiac disease: NYHA grade 3-4
2. CNS involvement at diagnosis
3. Uncontrolled serious infection
4. Impaired liver (transaminases >3x normal upper limit or bilirubin > 1.5 x normal upper limit, unless due to Gilbert´s syndrome), renal (GFR<30ml/min) or other organ function not caused by lymphoma, which will interfere with the treatment
5. Absolute neutrophil count (ANC) <1000 cells/mcL or platelets <100,000 cells/mcL, unless due to lymphoma
6. Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma, unless treated with curative intent, and without relapse since 2 years, or low grade prostate cancer, not in need of treatment
7. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study
8. Known hypersensitivity to rituximab, polatuzumab vedotin, cyclophosphamide, vincristine or doxorubicin, or to additives in the formulations above, or known hypersensitivity to other human, humanized, chimeric or porcine monoclonal antibodies, or HACA against rituximab
9. Peripheral neuropathy grade ≥ 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival: This is defined as the interval between randomization date and date of documented progression, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepont of evaluation is when the last patient included in the study has been followed for a minimum of 2 years |
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E.5.2 | Secondary end point(s) |
Overall survival: This is defined as time from registration to death of any cause. Patients still alive or lost to follow-up are censored at the last date they were known to be alive.
Lymphoma specific survival: This is defined as the time interval from inclusion in the study to lymphoma associated death and will be censored at the latest follow-up date in patients alive.
Response duration: Duration of best response from time of response assessment to progression or lymphoma associated death
Complete remission rate (CR): Number and fraction of patients included achieving a CR. Overall remission rate: Number and fraction of patients included achieving a complete or partial remission.
Health related quality of life (HRQOL) will be assessed through patient recorded questionnare EORTC-QLQ-C30 Safety through Collection of adverse events and serious adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepont of evaluation of efficacy endpoints (overall survival, lymphoma specific survival, overall remission rate, response duration) is when the last patient included in the study has been followed for a minimum of 2 years.
Evaluation of adverse and serious adverse events will be performed when the first 50 patients have been followed for a minimum of 3 months and further throughout the study when deemed necessary. Evaluation of these events will be recorded for the entire study population at the same time as the efficacy assessments.
Health related quality of life (HRQOL) will be recorded when the last patient included has been followed for at least 12 months after end of treatment. |
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
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 | 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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 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 |