E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient has a history of DLBCL according to the WHO classification. with progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore the antitumor activity of panobinostat in term of overall response (OR) at the end of the induction phase (i.e. month 6 from the beginning of panobinostat) |
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E.2.2 | Secondary objectives of the trial |
1. To explore the antitumor activity of panobinostat in terms of Complete Response (CR) 2. To assess the time to response (TTR) 3. To evaluate Progression Free Survival (PFS) 4. To assess the safety and tolerability of panobinostat 5. To evaluate the Overall Survival (OS) |
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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 |
FARMACOGENETICA: Versione: Data: Titolo:PHARMACOGENETICS STUDIES Obiettivi:The general aim of the study is twofold:
1. Explore the impact of pharmacogenetics on efficacy and toxicity of panobinostat in DLBCL.
The specific aims of the study are as follows:
1. Genotype DLBCL patients for SNPs of genes that are implicated in drug metabolism, detoxification, transport, targeting of panobinostat
2. Correlate SNP genotype with the primary efficacy endpoint of panobinostat, namely overall response rate
3. Correlate SNPs genotype with panobinostat toxicities
ALTRI SOTTOSTUDI: - HISTOPATOLOGY AND GENE EXPRESSION PROFILING STUDIES
- TELOMERE BIOLOGY
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E.3 | Principal inclusion criteria |
1. Patient age is ≥ 18 years 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 3. Patient has a history of DLBCL according to the WHO classification 4. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT 5. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT 6. Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy 7. Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement 8. Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail): • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L [SI units 1.5 x 109/L] • Platelet count ≥ 100 x 109/L • Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution • Serum creatinine ≤ 1.5 x ULN • Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome) • AST/SGOT and/or ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement 9. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism 10. Written informed consent was obtained from the patient prior to any study-specific screening procedures 11. Patient has the ability to swallow capsules or tablets 12. Practice acceptable birth control |
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E.4 | Principal exclusion criteria |
1. Patient age is ≥ 18 years 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 3. Patient has a history of DLBCL according to the WHO classification 4. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT 5. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT 6. Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy 7. Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement 8. Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail): • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L [SI units 1.5 x 109/L] • Platelet count ≥ 100 x 109/L • Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution • Serum creatinine ≤ 1.5 x ULN • Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome) • AST/SGOT and/or ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement 9. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism 10. Written informed consent was obtained from the patient prior to any study-specific screening procedures 11. Patient has the ability to swallow capsules or tablets 12. Practice acceptable birth control Exclusion criteria 1. Patient has a history of prior treatment with a DAC inhibitors including panobinostat 2. Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment 3. Patient has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment 4. Patient has been treated with any other anti lymphoma therapy within 3 weeks of start of study treatment 5. Patient is using any anti-cancer therapy concomitantly 6. Patient has been treated with > 5 prior systemic lines of treatment 7. Patient has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment 8. Patient treated with allogeneic hematopoietic stem cell transplant with active progressive cGVHD; patient has received DLI ≤ 6 weeks prior to start of study treatment; patient is planned to receive DLI 9. Patient has a history of another malignancy ≤ 3 years before study entry, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix 10. Patient has a history of CNS involvement with lymphoma 11. Patient has impaired cardiac function including any of the following: • Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beat |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
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 | Yes |
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 | No |
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) | 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 | 16 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |