| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/refractory classical Hodgkin's lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed/refractory classical Hodgkin's lymphoma |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020206 |
| E.1.2 | Term | Hodgkin's disease |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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.
As of amendment 3, the primary objective of this trial has been met. The purpose of this amendment is to continue to provide study drug to patients currently deriving clinical benefit from treatment with panobinostat on this study, per investigator assessment, and to monitor safety while on treatment. |
|
| E.2.2 | Secondary objectives of the trial |
• 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
As of amendment 3, Investigators will follow and assess efficacy locally only, as per SOC for patients with HL. |
|
| E.2.3 | Trial contains a sub-study | No |
| 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 classical HL (i.e. Nodular sclerosing, Mixedcellularity, Lymphocyte-rich, Lymphocyte depleted)
4. Patient has progressive disease after receiving high dose chemotherapy with AHSCT.
Note: If last therapy was ≥ 18 months ago, then a biopsy should be performed to confirm diagnosis.
Note: Patient should have received <=5 prior systemic treatment regimens (See PTS 2 for definitions and examples)
5. Patient has at least one site of measurable nodal disease at baseline≥ 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).
Note: Patients with bone marrow involvement are eligible, but this criterion alone should not be used for disease measurement.
6. 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 10exp9/L [SI units 1.5 x 10exp9/L]
• Platelet count ≥ 75 x 10exp9/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. Postcorrection values must not be deemed to be a clinically significant abnormality prior to patients being dosed.
• 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
7. Clinically euthyroid
Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
8. Written informed consent was obtained from the patient prior to any study-specific screening procedures
9. Patient has the ability to swallow capsules or tablets |
|
| 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 ≤ 2 weeks prior to starting study drug or whose side effects of such therapy have not resolved to ≤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 ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to ≤ grade 1
7. Patient is using any anti-cancer therapy concomitantly
8. Patient treated with allogeneic hematopoietic stem cell transplant who is currently on, or has received immunosuppressive therapy within 90 days prior to start of screening and/or have ≥ Grade 2 graft versus host disease (GvHD).
9. Patient has a history of another primary 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 beats per minute), QTcF > 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
• Presence of unstable atrial fibrillation (ventricular heart rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
• Previous history angina pectoris or acute MI within 6 months
• Congestive heart failure (New York Heart Association functional classification III-IV)
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 ≥ 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 history of HIV seropositivity (screening HIV testing is not required)
17. 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
18. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined
as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). WOCBP must have a negative serum pregnancy test at baseline.
19. 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• CT scan to assess the response rate and for monitoring for progression
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| There will be no further efficacy data captured other than documentation of the date of disease progression as assessed by investigator and death on study, as applicable |
|
| E.5.2 | Secondary end point(s) |
• Safety
• Pharmacokinetic parameters: Cmax, Tmax, and AUC0-24
• Exploratory FDG-PET scan response and exploratory biomarkers
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Laboratory and other safety assessments will be reduced to that which is appropriate to adequately monitor and protect patient safety. Patients will have their data further summarized and/or listed as applicable in a subsequent extension report once these patients have either completed or discontinued the study. |
|
| 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 | 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| 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 | 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 | 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 |
| Australia |
| Belgium |
| Brazil |
| France |
| Germany |
| Israel |
| Italy |
| Malaysia |
| New Zealand |
| Singapore |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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