E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse-large B cell lymphoma (DLBCL) |
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E.1.1.1 | Medical condition in easily understood language |
A subtype of non-Hodgkin lymphoma, a tumour disease involving B lymphocytes, a particular type of white blood cells with a key role in immune system |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Assessment of rate of complete remission after induction therapy |
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E.2.2 | Secondary objectives of the trial |
Assessment of: overall survival, progression-free survival, cardiac toxicity, and safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained according to international guidelines and local laws 2. Male or female patients aged ≥ 18 years without upper age limit 3. Previously untreated and histologically confirmed diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma grade 3B according to REAL/WHO classification 4. At least one objectively bi-dimensionally measurable lesion as demonstrated by CT, spiral CT, or MRI that can be followed for response as target lesion; patients with the following sites of disease are NOT eligible: - Patients with only skin lesions or only palpable lymph nodes - Patients with spleen or bone marrow as only site of disease 5. Life expectancy ≥ 3 months according to investigator´s opinion 6. Ann Arbor stage: II-IV 7. Ability to understand the nature of the trial and the trial-related procedures and to comply with them 8. Criteria for stratification: Population 1: Age ≥ 75 years (without limited cardiac function) not eligible for standard R-CHOP 21 treatment or Population 2: Impaired cardiac function, characterised by: First 10 patients: Ejection fraction: ≥ 40% and ≤ 50%
Additional patients: Ejection fraction: > 30% and ≤ 50%
Note: Patients ≥ 75 years of age with impaired cardiac function are eligible for population 2.
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E.4 | Principal exclusion criteria |
1. Severe pulmonary, hepatic or renal comorbidities which make the patient ineligible for cytotoxic drug treatment 2. Severe cardiac impairment, e.g. NYHA class IV, (with the exception of inclusion criterion 8), or resting cardiac troponin T levels >0.05 ng/ml (according to > grade 1 CTCAE 3.0) which makes the patient ineligible for cytotoxic drug treatment 3. Prior treatment for lymphoma other than pre-treatment with steroids 4. History of indolent lymphoma 5. Manifestation of DLBCL disease in central nervous system (CNS) 6. Active hepatitis B or C, serologic positivity for HIV infection 7. HIV-related lymphoma 8. Immunisation with live virus vaccines within the last 14 days 9. Major thoracic and/or abdominal surgery within the 4 weeks before trial registration from which the patient has not fully recovered except for diagnosis of non-Hodgkin lymphoma (NHL); patients who have had minor surgery may be enrolled after a ≥ 1 week recovery period except for diagnosis of NHL 10. Serious (NCI CTCAE grade 3-4) intercurrent infection at the time of trial registration or deep-seated or systemic mycotic infection. 11. Active or history of another malignancy except cured basal cell carcinoma of skin or carcinoma in situ of uterine cervix; patients who have been in remission from another previous malignancy for > 5 years will be considered eligible 12. Known hypersensitivity to pixantrone, or any drugs or excipients of the associated chemotherapy R-CPOP that the patient will receive 13. Simultaneous participation in other interventional trials and/or participation before the end of a required restriction period 14. Participation in a clinical trial within the last 30 days before being registered in this trial 15. Known or persistent abuse of medication, drugs or alcohol 16. Person who is in a relationship of dependence/employment with the sponsor or the investigator 17. For female patients of child-bearing potential: current or planned pregnancy, nursing period 18. Unwillingness to use an adequate contraception method during chemotherapy treatment until six months thereafter: for male patients (unless vasectomised): 18.1 a latex condom during sexual contact with females of childbearing potential for female patients of child-bearing potential: 18.2 mechanical method (female condom, diaphragm or coil) used in combination with a spermicide; hormonal intra-uterine device or hormonal contraception in combination with a mechanical method of contraception
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of complete remission after induction therapy as determined by PET-CT 6 weeks after last treatment (EOT visit) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall survival: time from start of trial treatment to death from any cause, considering patients, where the event of interest has not been observed, as censored observations.
Progression-free survival: time from start of trial treatment to disease progression or death from any cause, whichever occurs first. Patients for whom the event of interest has not been observed are analysed as censored observations.
Cardiac toxicity: echocardiography, ECG, troponin T, NT-proBNP during chemotherapy, at end of treatment and every 3 or 6 months during follow up; cardiac AEs according to CTCAE
Safety: Rates of adverse events and serious adverse events according to CTCAE |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
endpoints: Overall survival: continuously during treatment and follow-up Progression-free-survival: continuously during treatment and follow-up Cardiac toxicity: continuously during treatment and follow-up Safety: continously during treatment phase |
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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 | 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) | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |