Clinical Trial Results:
Phase II clinical study on the activity of salvage therapy with high doses of oral clarithromycin in patients with extranodal marginal zone relapsed or refractory lymphoma
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Summary
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EudraCT number |
2011-004808-37 |
Trial protocol |
IT |
Global end of trial date |
15 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Dec 2025
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First version publication date |
20 Dec 2025
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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 |
HD-K
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
IRCCS San Raffaele
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Sponsor organisation address |
Via Olgettina 60, Milano, Italy, 20132
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Public contact |
Unita' Operativa Linfomi, Fondazione San Raffaele del Monte Tabor, +39 0226437649, ferreri.andres@hsr.it
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Scientific contact |
Unita' Operativa Linfomi, Fondazione San Raffaele del Monte Tabor, +39 0226437649, ferreri.andres@hsr.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 |
31 Dec 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Jul 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jul 2013
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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 |
The main objective is to evaluate the activity of oral clarithromycin high-dose (2 g/day) in patients with extranodal marginal zone relapsed / refractory lymphoma.
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Protection of trial subjects |
The patient’s confidentiality will be maintained and will not be made publicly available to the extent permitted by the applicable laws and regulations (Low n. 675/1996 and amendments) and Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation).
An identification number will be automatically attributed to each patient enrolled in the trial. This number will identify the patient and must be included on all case report forms. In order to avoid identification errors, date of birth will also be reported on forms.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jan 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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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) |
5
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From 65 to 84 years |
17
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85 years and over |
1
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Recruitment
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Recruitment details |
From November 2011 to October 2013 , we enrolled 23 patients | ||||||
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Pre-assignment
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Screening details |
Both male and female were included ( >18 years), each with histological diagnosis of extragastric or gastric extranodal marginal zone B-cell lymphoma Helicobacter pylori-positive refractory to conventional antibiotic therapy or H. pylori-negative. Written informed consent. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
23 | ||||||
Number of subjects completed |
23 | ||||||
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Period 1
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Period 1 title |
HD-K treatment (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Clarithromycin | ||||||
Arm description |
The proposed strategy involves the administration of home antibiotic therapy with clarithromycin (Klacid®) in the form of 500 mg tablets to be taken orally. Clarithromycin is a macrolide antibiotic, commonly used in infections of the upper respiratory tract and community-acquired lung infections in immunocompetent hosts. The therapy will be administered as follows: patients will take 4 500 mg tablets of clarithromycin, all together, once a day (every 24 hours), orally, for 14 days, followed by a 7-day interval. The tablets will be taken, away from meals, with plenty of water and in a sitting or standing position, never in bed or as the last activity of the day. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
clarithromycin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Buccal use
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Dosage and administration details |
The therapy will be administered as follows: patients will take 4 500 mg tablets of clarithromycin, all together, once a day (every 24 hours), orally, for 14 days, followed by a 7-day interval. The tablets will be taken, away from meals, with plenty of water and in a sitting or standing position, never in bed or as the last activity of the day.
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Baseline characteristics reporting groups
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Reporting group title |
HD-K treatment
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Clarithromycin
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Reporting group description |
The proposed strategy involves the administration of home antibiotic therapy with clarithromycin (Klacid®) in the form of 500 mg tablets to be taken orally. Clarithromycin is a macrolide antibiotic, commonly used in infections of the upper respiratory tract and community-acquired lung infections in immunocompetent hosts. The therapy will be administered as follows: patients will take 4 500 mg tablets of clarithromycin, all together, once a day (every 24 hours), orally, for 14 days, followed by a 7-day interval. The tablets will be taken, away from meals, with plenty of water and in a sitting or standing position, never in bed or as the last activity of the day. | ||
Subject analysis set title |
all patients treated with HD-K
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full Analysis Set includes all patients who received at least one dose of HD-K and had at least one tumor response assessment. These patients are used to report baseline characteristics for the overall baseline period
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End point title |
overall response rate | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
from the start of treatment until the post-treatment response assessment
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Statistical analysis title |
Descriptive statistics | |||||||||
Statistical analysis description |
This is a single-arm phase II trial using a Simon minimax two-stage design. There is no comparator arm. Analyses for ORR, PFS, OS, and safety are descriptive. The system requires two groups by default, but only one arm is present.
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Comparison groups |
Clarithromycin v all patients treated with HD-K
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.05 [1] | |||||||||
Method |
Simon minimax two-stage design | |||||||||
Parameter type |
ORR=52%; 95%CI 32-72% | |||||||||
Confidence interval |
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95% | |||||||||
sides |
1-sided
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lower limit |
32 | |||||||||
upper limit |
72 | |||||||||
Variability estimate |
Standard deviation
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| Notes [1] - The Simon minimax two-stage design was used. The maximum ORR considered of low interest was 40% (P0) [11] and the minimum ORR considered of interest was 70% (P1). The target enrollment (α = 0.05; β = 0.20; two-sided) was estimated to be 21 patient |
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Adverse events information
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Timeframe for reporting adverse events |
All adverse events occurring from the first study-related procedure up to 30 days after the last dose of study drug
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTC AEs | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.3
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Reporting groups
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Reporting group title |
Adverse event
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Reporting group description |
Eighteen patients underwent treatment as scheduled; HD-K was interrupted in five patients due to nausea (n = 2) or progressive disease (n = 3); 79 (86%) of 92 planned courses were delivered. Tolerability was excellent; nausea was the commonest sideeffect, but it was manageable and did not require dose reduction, course each) were: grade-1 headache, grade-1 rash, grade-1 constipation, grade-2 join pain. Diarrhea was not recorded. No hemogram and biochemical abnormalities were detected during or after HD-K. Electrocardiogram abnormalities (i.e. QT prolongation, arrhythmias), often reported during macrolides use, were not recorded. | ||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||
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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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08 Apr 2013 |
eliminate the possibility of administering statins in combination with clarithromycin due to evidence of an increased risk of rhabdomyolysis. |
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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/25935794 |
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