| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with classical Hodgkine's Lymphoma (HL), who achieved a complete response following high dose chemotherapy (HDT) and autologous stem cell transplant (AHSCT). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020206 |
| E.1.2 | Term | Hodgkin's disease |
|
| 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 compare the disease free survival (DFS) in patients with HL after achieving a complete response following AHSCT with HDT who are treated with panobinostat versus those who receive placebo based on investigator’s review of radiological images |
|
| E.2.2 | Secondary objectives of the trial |
• To compare overall survival (OS) for the two arms
• To estimate and compare the rate of relapse (RoR) at 6, 12, and 24
months from randomization for the two arms
• To characterize the safety and tolerability of panobinostat |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient age is ≥ 18 years
2. Patient has a history of histologically confirmed classical HL (i.e. Nodular
sclerosing (NSHL), Mixed-cellularity (MCHL), Lymphocyte-rich (LRHL),
Lymphocyte depleted (LDHL))
3. Patient has achieved a complete response by CT/MRI scan within 9
weeks (± 1 week) from the day of their first autologous peripheral blood/
bone marrow stem cell transfusion (AHSCT) following HDT. Complete
response is defined as:
Normalization of all nodes and lesions compared to pre-transplant scan
performed prior to salvage therapy for relapse. Any residual abnormal
masses on the post transplant CT/MRI must be metabolically inactive on
a PET scan.
Note: If the first AHSCT was a tandem transplant, the 9 (+/- 1 week) will
be from the date of the second transfusion.
4. Patient has at least one of the following factors that places them at risk
for relapse:
• Primary refractory disease (including relapse in ≤ 3 months of
completion of 1st line treatment)
• First relapse >3 but <12 months from last dose of 1st line treatment
• Multiple relapses (prior to transplant)
• Stage III/IV disease (at relapse, prior to transplant)
• Hemoglobin <10.5 gm/dL (at relapse, prior to transplant)
5. Patient has an Eastern Cooperative Oncology Group (ECOG)
performance status of ≤ 2
6. Patient has the following laboratory values within 3 weeks prior to
starting study drug (labs may be repeated, if needed, to obtain
acceptable values before failure at screening is concluded)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
• Platelet count ≥ 100 x 109 /L
• AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
• Serum total bilirubin ≤ 1.5 ULN
• Serum creatinine ≤ 1.5 x ULN
• Serum potassium, magnesium, phosphorus, sodium, total calcium
(corrected for serum albumin) or ionized calcium within normal limits
Note: Potassium, magnesium, sodium and/or phosphorus supplements (but
not platelet or RBC transfusions) may be given to correct values that are <
lower limit of normal (LLN). Post-correction values must not be deemed to be
a clinically significant abnormality prior to patients being dosed.
7. Patient has the ability to swallow capsules
8. Sexually active patient (men and women of child bearing potential
{WOCBP}) agrees to use double barrier method of contraception during
the course of the study treatment period (13 cycles) and for 3 months
after completing study treatment. 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.
9. Patient has signed informed consent prior to any screening procedures |
|
| E.4 | Principal exclusion criteria |
1. Patient has been treated with allogeneic transplant
2. Patient has received any anti-lymphoma therapy after AHSCT including
but not limited to:
• chemotherapy prior to start of study
• biologic immunotherapy including monoclonal antibodies or
experimental therapy prior to start of study
• radiation therapy
3. Patient has not recovered from reversible toxicity due to any prior
therapies (e.g. returned to baseline or Grade ≤1) except for
hematological laboratory parameters
Note: Patient does not meet this criteria if the toxicity is stable and
irreversible, and there is no evidence that panobinostat causes a similar
toxicity
4. Patient has received prior treatment with DAC inhibitors including
panobinostat
5. Patient has received an investigational agent of any kind within 28 days
of randomization
6. Patient taking any anti-cancer therapy concomitantly
7. Patient needs valproic acid within 5 days prior to first administration of
panobinostat/ study treatment
8. Patients with evidence of another malignancy not in remission or history
of such a malignancy within the last 3 years (except for treated basal or
squamous cell carcinoma, or in situ cancer of the cervix).
9. Patient has undergone major surgery ≤ 2 weeks prior to starting study
drug or who have not recovered from side effects of such therapy to <
grade 1 CTCAE or baseline
10. Patient has impaired cardiac function, including any one of the following:
• Left ventricular ejection fraction (LVEF) < the lower limit of
institutional norm, as determined by echocardiogram (ECHO) or
multiple uptake gated acquisition scan (MUGA)
• Obligate use of a permanent cardiac pacemaker
• Congenital long QT syndrome
• History or presence of ventricular tachy-arrhythmias
• Resting bradycardia defined as < 50 beats per minute
• QTcF > 480 msec on screening ECG
• Complete left bundle branch block, bifasicular block
• Any clinically significant ST segment and/or T-wave abnormalities
• Presence of unstable atrial fibrillation (ventricular response rate >
100 bpm). Patients with stable atrial fibrillation are allowed in the
study provided they do not meet the other cardiac exclusion criteria.
• Myocardial infarction or unstable angina pectoris ≤ 6 months prior to
starting study drug
• Congestive heart failure (New York Heart Association class III-IV)
• Other clinically significant heart disease and vascular disease (e.g.
uncontrolled hypertension)
11. Patient is taking medications with relative risk of prolonging the QT
interval or inducing torsade de pointes, if such treatment cannot be
discontinued or switched to a different medication prior to starting study
drug
12. Patient has impairment of gastrointestinal (GI) function or GI disease that
may significantly alter the absorption of panobinostat, such as:
• ulcerative disease
• uncontrolled nausea
• vomiting
• diarrhea CTCAE grade ≥ 2 (despite antidiarrheal medications)
• malabsorption syndrome
• obstruction
• stomach and/or small bowel resection
13. Patient has any other concurrent severe and/or uncontrolled medical
conditions that could cause unacceptable safety risks or compromise compliance with the protocol such as:
• uncontrolled diabetes
• active or uncontrolled infection
• chronic obstructive or chronic restrictive pulmonary disease
including dyspnea at rest from any cause
• uncontrolled thyroid dysfunction
• recent, acute or active bleeding
14. Patient has a known history of human immunodeficiency virus (HIV)
seropositivity or history of active/treated hepatitis B or C (a test for
screening is not required)
15. Women who are pregnant or breast feeding |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Disease Free Survival (DFS) |
|
| 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) | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | 22 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 74 |
| 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 |
|
| 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 | 5 |
| 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 | 5 |
| 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 |
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