Clinical Trial Results:
A phase II study of oral Panobinostat in adult patients with relapsed/refractory diffuse large B-cell lymphoma after high-dose chemotherapy with autologous stem cell transfusion (ASCT) or in adult patients who are not eligible for ASCT
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Summary
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EudraCT number |
2011-000175-13 |
Trial protocol |
IT |
Global end of trial date |
03 Apr 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Aug 2022
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First version publication date |
21 Aug 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
FIL_PanAL10
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01523834 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fondazione Italiana Linfomi (FIL) ONLUS
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Sponsor organisation address |
Piazza Turati 5, Alessandria, Italy,
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Public contact |
Segreteria, Fondazione Italiana Linfomi ONLUS, +39 0131/033151, segreteriadirezione@filinf.it
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Scientific contact |
Segreteria, Fondazione Italiana Linfomi ONLUS, +39 0131/033151, segreteriadirezione@filinf.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Feb 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Jan 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Apr 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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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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Protection of trial subjects |
For patients who are unable to tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to keep the patient on study drug. These dose adjustments comprise delays in dosing and/or reductions in the dose being administered. Dosing should always be temporarily discontinued if the physician determines it is in the best interest of the patient. All dose modifications must be recorded on the Dosage Administration Record form.
The dose of panobinostat may be modified for a patient during any cycle. The first dose adjustment consists in the modification of panobinostat administration from three times every week (QW) to three times every other week (QOW). Subsequent dose adjustments consist in panobinostat dose reductions. Dosages lower than 30 mg three times QOW are not permitted. When and if it is determined that a patient would require a dose below 30 mg QOW, the patient should be discontinued from study treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Jun 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 35
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Worldwide total number of subjects |
35
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EEA total number of subjects |
35
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
11
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From 65 to 84 years |
24
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85 years and over |
0
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Recruitment
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Recruitment details |
Thirtyfive patients recruited in Italy from 14th June 2011, with date of last completed at 3rd April 2017. | ||||||||||||||
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Pre-assignment
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Screening details |
Adult patients with R/R DLBCL who previously received at least two lines of treatments including ASCT consolidation or patients with PD after a single first line R-CHOP if not eligible for ASCT because of age or co-morbidities. All patients must satisfy all the inclusion criteria and none of exclusion criteria. | ||||||||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Single arm | ||||||||||||||
Arm description |
Patients will receive panobinostat. The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). The duration of a treatment course will be 28 days. The first dose of panobinostat in course 1 defines day 1 of the treatment cycle, and each cycle thereafter will begin 28 days later. | ||||||||||||||
Arm type |
Single arm study | ||||||||||||||
Investigational medicinal product name |
Panobinostat
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Investigational medicinal product code |
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Other name |
LBH589
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Panobinostat should be taken p.o. at the dose of 40mg/day three-times every week (QW),as part of 28 days treatment cycle.
Induction phase
Patients will receive panobinostat for 6 courses.Response assessment will be performed every 2 courses until the end of the induction phase.Patients with responsive (CR/PR) or stable disease during each assessment will complete the induction phase.
Consolidation phase
Response assessment will be performed every 3 courses until course 12.Patients with responsive or stable disease will continue with maintenance.
Maintenance phase
Patients will continue therapy until disease progression, intolerability, withdrawal of consent and/or if the investigator determines that further therapy is not in the patient’s best interest. Response assessment will be performed every three courses until course 36.For patients still in therapy after course 36,the subsequents response assessments will be performed according to each institutional policy.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single arm
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Reporting group description |
Patients will receive panobinostat. The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). The duration of a treatment course will be 28 days. The first dose of panobinostat in course 1 defines day 1 of the treatment cycle, and each cycle thereafter will begin 28 days later. | ||
Subject analysis set title |
Subject analyzed
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Thirtyfive patients recruited in Italy from 14th June 2011, with date of last completed at 3rd April 2017.
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End point title |
Overall Response Rate (ORR) | ||||||||||||
End point description |
ORR is defined as the proportion of patients achieving a Complete Response (CR) or Partial Response (PR) according to the Cheson 1999 response criteria
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End point type |
Primary
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End point timeframe |
At the end of the induction phase (i.e. month 6 from the beginning of panobinostat)
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Statistical analysis title |
Overall Response Rate (ORR) | ||||||||||||
Comparison groups |
Single arm v Subject analyzed
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Frequency percent (%) | ||||||||||||
Point estimate |
17.1
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Confidence interval |
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95% | ||||||||||||
sides |
1-sided
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lower limit |
7.8 | ||||||||||||
upper limit |
- | ||||||||||||
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End point title |
Time to Response (TTR) | ||||||||||||
End point description |
TTR is defined as the time from enrolment to Overall Response
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End point type |
Secondary
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End point timeframe |
36 months
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| Notes [1] - Only 6 responders [2] - Only 6 responders |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression Free Survival (PFS) | ||||||||||||
End point description |
The Progression Free Survival (PFS) is defined as the time from enrolment to disease progression or death from any cause.
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End point type |
Secondary
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End point timeframe |
50% of survival
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) | ||||||||||||
End point description |
The Overall Survival (OS) is defined as the time from enrolment to death from any case
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End point type |
Secondary
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End point timeframe |
50% survival
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
6 years
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Adverse event reporting additional description |
Common Terminology Criteria for Adverse Events (CTCAE Version 4.0). For non-serious adverse events all grade.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Single arm
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Reporting group description |
Patients will receive panobinostat. The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). The duration of a treatment course will be 28 days. The first dose of panobinostat in course 1 defines day 1 of the treatment cycle, and each cycle thereafter will begin 28 days later. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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07 Feb 2012 |
Change in the legal representative of the Fondazione Italiana Linfomi Onlus |
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29 Aug 2016 |
Changes to the protocol and synopsis: clarification on the definition of the conclusion of the study, updating of contact details, correction of typos.
In addition, with this amendment proceeds to:
- Update of the Investigator Brochure: new version no. 12.1 of 06/28/2016;
- Change of PI hematology center of IRCCS A.O.U. San Martino-IST di Genova (updated list of centers v. 3 of 25 July 2016).
The amendment is intended only for the centers still open in Alessandria (coordinator) and in Genova Dott.ssa Congiu. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29616865 |
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