E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapse of aggressive non-Hodgkin lymphoma of B and T-cell phenotype |
Uusiutunut aggressiivinen non -Hodgkin (B- ja T-solu) lymfooma |
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E.1.1.1 | Medical condition in easily understood language |
Relapse of lymphoma of B or T cell type |
Uusiutunut B- tai T- solulymfooma |
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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 | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025321 |
E.1.2 | Term | Lymphomas non-Hodgkin's T-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the MTD of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in "fit" patients with rel aNHL of B- or T-cell phenotype.
Evaluate the ORR and PFS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide and bendamustine either at the identified MTD (P(R)EBEN- fit) in "fit"patients or at the baseline dose level (P(R)EBEN) in "frail" patients with rel aNHL.
Evaluate the CR, PR, duration of response, and OS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with B-or T-cell NHL.
Evaluate the safety and tolerability of combination therapy with pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with aggressive B- or T-cell NHL. |
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E.2.2 | Secondary objectives of the trial |
To perform molecular analyses at nucleic acid (DNA, RNA, microRNA) and protein level to see if specific molecular features can predict responder versus non-responder status. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with a histologically confirmed relapse of an aggressive lymphoma of T- or B-cell phenotype (including follicar lymphoma grade 3b). For excluded hidstological entities see"Exclusion Criteria"
.Phase 1 + Phase 2"fit" patients
- Age 18 - 70 years at the time of inclusion
- ECOG performance score(PS) 0-1 at protocol entry ( for ECOG definition, see appendix A) and/ or
- ECOG PS 2-3 at the protocol entry (for ECOG definition, see appendix A) and/ or
- Deemed "frail" by the treating physician
- Estimated life expectancy of 3 months or longer
- Measurable disease
- Hemoglobin ≥ 8g/dL (≥ 5 mmol/l) (can be post transfusion)
- Platelets ≥ 100 x 109 / L; ≥ 75 x 109/ L permitted if bone marrow involvement
- Absolute netrophil count ≥ 1.5 x 109 / L; ≥ 1.0 x 109 / L permitted if documented bone marrow involvement
- Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); patients with proven Gilbert's syndrome ( ≤ 5 x ULN) may be enrolled.
- Serum glutamic-oxaloacetic transaminase (AST) and / or serum glutamic-pyruvic tranaminase (ALT) ≤ 2.5 X ULN, or ≤ 5 x ULN if elevation is due to hepatic involvement by lymphoma
- Serum creatinine ≤ 2 x ULN
- Written informed consent |
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E.4 | Principal exclusion criteria |
- Patient swith primary refratory disease (e.g. prigressing under platinum-containing of similar salvage therapy) defined as < 6 months response duration from last given course of treatment
- High-dose thearpy with autologous stem cell rescue within the last 6 months prior to study entry.
- Following T-cell lymphoma entities:
- T-cell lymphoblastic lymphoma
- Hepatosplenic T-cell lymphoma
- Extranodal NK/ T, nasal type
- Subcutaneous panniculities-like
- Primary cutaneous T-cell lymphoma
- Primary leukemic T-cell lymphoma
- Following B-cell lymphoma entities:
- Transformed indolent B-cell lymphomas
- Post-transplant B-cell lymphoproliferstive disease
- HIV associated B-cell lymphoma
- Concurrent severe and / or uncotrolled medical disease which is not lymphoma-related
- Left ventricular ejection fraction (LVEF) < 45 %
- Suspected or documented central nervous system involment By NHL.
- Patients known to be antigen positie for HIV and / or hepatis B and / or hepatitis C
- Patients with active, uncontrolled infections
- History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carsinoma
- Known hypersensitivity to one or more of the study drugs
- Unwillingness or inability to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 part of the trial: MTD of pixantrone, bendamustine and etoposide in "fit" rel aNHL pts
Phase 2 part of the trial: ORR in both "fit" and "frail" rel aNHL pts |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1 part of the trial: End of treatment cycle 2 of the last included patient
Phase 2 part of the trial: End of treatment |
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E.5.2 | Secondary end point(s) |
Phase 1 part of the trial:
- ORR
- CRR
- Duration of response (DOR)
Phase 2 part of the trial:
- Safety and tolerability of the P(R)EBEN combination regimen
- CRR
- DOR
- PFS
- OS
- Successful bridging to allogenetic transplantation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of treatment and after 5 years of follow-up |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose-finding phase 1b study |
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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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
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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
|
Last follow-up visit of the last subject |
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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 | 7 |
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 | 7 |
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 |