Clinical Trial Results:
A multicentre, phase II, open label, single arm study of pixantrone in patients with CD20-positive relapsed or refractory aggressive non-Hodgkin lymphoma treated with rituximab, ifosfamide and etoposide.
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Summary
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EudraCT number |
2017-000719-17 |
Trial protocol |
FR BE |
Global end of trial date |
19 Dec 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2026
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First version publication date |
29 Mar 2026
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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 |
PIVeR
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03458260 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
LYSARC
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Sponsor organisation address |
CH Lyon Sud – Bat 2D - 69495 PIERRE-BENITE Cedex - France, PIERRE-BENITE , France, 69495
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Public contact |
Clinical Project Manager N. PRONINA, LYSARC, +33 (0)427 01 27 38, piver@lysarc.org
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Scientific contact |
Pr. L. Fornecker, LYSARC, +33 (0)427 01 27 38, lm.fornecker@icans.eu
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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 |
24 Dec 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2024
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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 primary objective is to assess the efficacy of Pixantrone with rituximab, ifosfamide and etoposide as measured by the overall metabolic response (OMR) rate after 2 cycles of treatment or at permanent treatment discontinuation, whichever occurs first.
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Protection of trial subjects |
sentence on rescue treatment ?
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Background therapy |
Anthracycline-based regimens in combination with Rituximab are the standard of care in first-line for aggressive NHL. However, 30-40% will be refractory to first-line therapy or relapsed after standard first-line immunochemotherapy (R/R patients). Salvage chemotherapy followed by high-dose therapy and autologous stem-cells transplantation (HDT-ASCT) is the standard of care for eligible R/R patients. | ||
Evidence for comparator |
There is currently no standard of care for patients with R/R aggressive NHL who are not eligible for HDT-ASCT procedure. Studies have demonstrated the possibility to combine Pixantrone with rituximab and other chemotherapeutic compounds in indolent and aggressive NHL. The combination of Rituximab, Ifosfamide and Etoposide is the backbone of several salvage regimens for relapsed/refractory DLBCL and will be tested in this study. | ||
Actual start date of recruitment |
01 Jan 2018
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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 |
France: 71
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Country: Number of subjects enrolled |
Belgium: 3
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Worldwide total number of subjects |
74
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EEA total number of subjects |
74
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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) |
17
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From 65 to 84 years |
55
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85 years and over |
2
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Recruitment
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Recruitment details |
Enrollment of PIVeR study was to be stopped once 84 evaluable patients were enrolled with an estimated recruitment period of 3 years. However, the recruitment was not as efficient as expected and it has been stopped on December 31st, 2021. A total of 74 patients were enrolled. | ||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 74 patients were enrolled. 16 patients were screen failed | ||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
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 | ||||||||||||||||||||||||||||||||
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Arms
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Arm title
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Pixantrone - rituximab - ifosfamide - etoposide | ||||||||||||||||||||||||||||||||
Arm description |
Treatment will consist of 2 to 6 cycles of Pixantrone with rituximab, ifosfamide and etoposide (21-day cycle) | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Pixantrone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Dose for patients aged 18-69 : 80 mg/m2
Dose for patients aged 70 and + : 60 mg/m2
After reconstitution should be administered as a slow IV infusion over a period of 1 hour (+/- 10 minutes)
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Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Dosage 375 mg/m2
Administration : Chemotherapy products have been used according to summary of product characteristics.
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Investigational medicinal product name |
Ifosfamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for concentrate for solution for infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Chemotherapy products have been used according to summary of product characteristics.
Dose for pateints aged 18-69 : 1500 mg/m2
Dose for patients aged 70 and + : 1000mg/m2
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Investigational medicinal product name |
Etoposide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for dispersion for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Chemotherapy products are to be used according to summary of product characteristics.
Dosage for patients aged 18-69 : 150 mg/m2
Dosage for patients aged 70 and + : 100 mg/m2
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pixantrone - rituximab - ifosfamide - etoposide
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Reporting group description |
Treatment will consist of 2 to 6 cycles of Pixantrone with rituximab, ifosfamide and etoposide (21-day cycle) | ||
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End point title |
OMR rate after 2 cycles according to local investigator [1] | ||||||||
End point description |
Overall Metabolic Response rate by local investigator based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014).
Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders.
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End point type |
Primary
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End point timeframe |
After 2 cycles or at permanent treatment discontinuation, whichever occurs first.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The PIVeR trial was designed in order to detect an OMR increase in favor of the Pixantrone from 40% (null hypothesis) to 55% (alternative hypothesis), assuming an 80% power at a 5% (1-sided) significance level using a two-stage phase II design. The null hypothesis was to be rejected if the lower limit of the 90%CI was ≥ 40%. |
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| No statistical analyses for this end point | |||||||||
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End point title |
CMR rate after 2 cycles according to local investigator | ||||||||
End point description |
Complete Metabolic Response rate by local investigator based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014).
Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders.
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End point type |
Secondary
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End point timeframe |
After 2 cycles or at permanent treatment discontinuation, whichever occurs first.
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| No statistical analyses for this end point | |||||||||
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End point title |
OMR rate after 2 cycles according to central review | ||||||||
End point description |
Overall Metabolic Response rate according to central review based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014).
Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders.
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End point type |
Secondary
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End point timeframe |
After 2 cycles or at permanent treatment discontinuation, whichever occurs first.
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| No statistical analyses for this end point | |||||||||
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End point title |
OMR rate at the timepoint of interest according to local investigator | ||||||||
End point description |
Overall Metabolic Response rate by local investigator based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014).
Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders.
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End point type |
Secondary
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End point timeframe |
After 2 cycles, for patients who did not respond after 2 cycles.
After 2 cycles, for patients responders after 2 cycles and eligible for ASCT.
After 6 cycles, for patients responders after 2 cycles and not eligible for ASCT.
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| No statistical analyses for this end point | |||||||||
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End point title |
OMR rate at the end of treatment according to local investigator | ||||||||
End point description |
Overall Metabolic Response rate by local investigator based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014).
Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders.
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End point type |
Secondary
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End point timeframe |
At the end of treatment or at permanent treatment discontinuation, whichever occurs first.
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival | ||||||||
End point description |
PFS is defined as the time (years) from inclusion into the study to the first observation of documented disease progression or death due to any cause.
If a subject has not progressed or died, PFS will be censored at the date of tumor assessment.
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End point type |
Secondary
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End point timeframe |
Since inclusion.
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Attachments |
PFS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
Overall survival will be measured (in years) from the date of inclusion to the date of death from any cause.
Alive patients will be censored at the date of last contact.
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End point type |
Secondary
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End point timeframe |
Since inclusion.
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Attachments |
OS |
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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 |
From the date of informed consent signature to 30 days after last drug administration.
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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 |
4.0
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Reporting groups
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Reporting group title |
Pixantrone - rituximab - ifosfamide - etoposide
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Reporting group description |
Treatment will consist of 2 to 6 cycles of Pixantrone with rituximab, ifosfamide and etoposide (21-day cycle) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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27 Jul 2018 |
Protovol v2.0
- addition of a third treatment cycle for patients eligible for autologous stem cell transplantation, prior to conditioning therapy. Initially, only two cycles were planned. The relatively long interval between the second cycle and transplantation allows for the administration of an additional cycle in routine practice. |
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03 Jan 2019 |
Protocol v3.0
- Patient age limitation to 80 years
- Modification of the pixantrone dose for patients 70 years of age or older: the IDMC recommends reducing the dose to 60 mg/m² for patients aged 70 years or older
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27 Sep 2024 |
Protocol v4.0
Reduction of the study duration to 6 years |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 | |||||||
