E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/Refractory Classical Hodgkins Lymphoma |
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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 | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's lymphoma |
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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 |
To determine the objective response rate to therapy with oral panobinostat in patients with refractory/relapsed classical HL using modified response criteria for malignant lymphoma (see Post-text supplement 1). |
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E.2.2 | Secondary objectives of the trial |
Secondary To determine response rate based on central review of CT scan/MRI To assess the time to response To assess the duration of response To evaluate progression-free survival, PFS rate at 6 month and 8 month To assess the safety and tolerability of panobinostat treatment To assess overall survival To characterize the PK of panobinostat, including the parent drug and any potential metabolite/s when feasible in at least 15 consenting patients with HL Exploratory To explore FDG-PET-based response in approximately 25 patients with HL, enrolled in the study, to assess the anti-tumor response as compared to CT scans To assess biomarkers such as interleukine-6 (IL-6) and thymus and activation-regulated chemokine (TARC) in peripheral blood pre- and post-treatment To assess biomarkers such as Akt in archival tissue when available To assess adaptive immunity and protein acetylation status of circulating T-cells pre and post treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient age is &#8805; 18 years 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of &#8804; 2 3. Patient has a history of classical HL (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted) 4. Patient has progressive disease after receiving high dose chemotherapy with AHSCT 5. Patient has progressive disease on or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen, after first relapse. Note: If last therapy was more than &#8805; 18 months ago, then a biopsy should be performed to confirm diagnosis. Note: Patients will be allowed on study who have also received an allogeneic hematopoietic stem cell transplant, however this therapy alone is not sufficient for inclusion into this study. 6. Patient has at least one site of measurable nodal disease at baseline &#8805; 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (MRI is allowed only if CT scan can not be performed). See Post-text supplement 1. Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement. 7. Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail): Absolute neutrophil count (ANC) &#8805; 1.5 x 10 9/L [SI units 1.5 x 109/L] Platelet count &#8805; 75 x 109/L Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, calcium, magnesium, sodium, and/or phosphorus supplements may be given to correct values that are <LLN. Post-correction values must not be deemed to be a clinically significant abnormality prior to patients being dosed. Serum creatinine &#8804; 1.5 x ULN Serum bilirubin &#8804; 1.5 x ULN (or &#8804; 3.0 x ULN, if patient has Gilbert syndrome) AST/SGOT and/or ALT/SGPT &#8804; 2.5 x upper limit of normal (ULN) or &#8804; 5.0 x ULN if the transaminase elevation is due to disease involvement 8. Clinically euthyroid Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism. 9. Written informed consent was obtained from the patient prior to any study-specific screening procedures 10. Patient has the ability to swallow capsules or tablets |
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E.4 | Principal exclusion criteria |
1.Patient has a history of prior treatment with a DAC inhibitor 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 received chemotherapy or any investigational drug or undergone major surgery &#8804; 2 weeks prior to starting study drug or whose side effects of such therapy have not resolved to &#8804; grade 1. 5.Patient has been treated with > 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples). 6.Patient has received prior radiation therapy &#8804; 4 weeks or limited field radiotherapy &#8804; 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to &#8804; grade 1. 7.Patient is using any anti-cancer therapy concomitantly 8.Patient has been treated with allogeneic hematopoietic stem cell transplant who has received immunosuppressive therapy within 90 days prior to start of screening and/or have &#8805; Grade 2 graft versus host disease (GvHD). 9.Patient has a history of another primary malignancy &#8804; 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 (see protocol for details). 12. Patient has any other clinically significant heart disease (e.g., uncontrolled hypertension). 13. Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection). 14. Patient has unresolved diarrhea &#8805; grade 2 15. Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol. 16. Patient has a known HIV seropositivity. 17. Patient has active bleeding diathesis or is currently being treated with therapeutic doses of sodium warfarin (Coumadin)or other vitamin K active agents Note: mini-dose of Coumadin (e.g., 1 mg/day) or anti-coagulants given to maintain intravenous line patency, as well as unfractionated or low molecular weight heparin therapy is permitted. 18. Patient is using medications that have a relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug 19. Patient is a woman who is pregnant or breast feeding, or a women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study through 3 months after the end of treatment. One of these methods of contraception must be a barrier method. 20. Male patient whose sexual partner(s) are WOCBP who are not willing to use a double method of contraception, one of which includes a condom, during the study and for 3 months after the end of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
overall response rate, as defined in Section 10.4.1. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
valutazione degli indicatori biologici |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |