Clinical Trial Results:
Phase I/II feasibility study combining Brentuximab Vedotin (Adcetris) with second line salvage chemotherapy (DHAP) in Hodgkin lymphoma patients refractory to first line chemotherapy or in first relapse who are eligible for high dose treatment followed by autologous peripheral blood stem cell transplantation
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Summary
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EudraCT number |
2012-003097-45 |
Trial protocol |
NL DK FR |
Global end of trial date |
21 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Aug 2022
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First version publication date |
10 Aug 2022
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Other versions |
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Summary report(s) |
Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study |
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 |
NL40688.018.12
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02280993 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Academic Medical Center
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Sponsor organisation address |
Meibergdreef 9, Amsterdam, Netherlands, 1105AZ
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Public contact |
Roberto Liu, Academic Medical Center, 00 31205665950, r.d.liu@amsterdamumc.nl
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Scientific contact |
Roberto Liu, Academic Medical Center, 00 31205665950, r.d.liu@amsterdamumc.nl
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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 |
Interim
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Date of interim/final analysis |
20 Dec 2016
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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 |
21 Sep 2020
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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 |
Phase II
• To demonstrate the efficacy and safety of BV in combination with DHAP as salvage treatment (establish the fraction of responding patients – metabolic CR – as judged by PET-CT after the third cycle, and establish the rate of grade ¾ non-hematological toxicity, including neurotoxicity).
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Protection of trial subjects |
The Data Safety Monitoring Board will advise the Principal Investigator and the Co-PI about the continuation of the study. The DSMB will evaluate the general progress and the feasibility of the study, the quality and completeness of the data, side effects and safety.
The DSMB consists of at least 3 members, among whom (at least) one statistician and minimally two physicians. The members of the DSMB are invited on personal title on the basis of their expert knowledge of the disease involved and/or the research methodology. Members of the DSMB will have ample experience with phase I/II clinical trials.
The members of the DSMB will not be involved in the study or work in a hospital department participating in the study.
The DSMB reports their written recommendations to the trial statistician. The report may consist of a confidential and a public part, where the confidential part contains references to unblinded data, if there are any. The trial statistician forwards the public part of the DSMB recommendation to the Principal Investigator and the Co-PI. The DSMB recommendations are not binding.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Sep 2013
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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 |
Netherlands: 35
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Country: Number of subjects enrolled |
Denmark: 3
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Country: Number of subjects enrolled |
France: 17
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Worldwide total number of subjects |
55
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EEA total number of subjects |
55
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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) |
54
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
During phase II a total of 55 patients were included in the period between 23-10-2015 and 25-07-2017. | ||||||
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Pre-assignment
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Screening details |
All patients provided written informed consent. The study enrolled patients aged ≥18 years with histologically confirmed CD30 positive cHL by local pathology assessment, either having primary refractory disease or a first relapse after first-line chemotherapy. Central pathology review was performed by two experienced hematopathologists. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
55 | ||||||
Number of subjects completed |
55 | ||||||
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Period 1
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Period 1 title |
Phase II (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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Salvage treatment during phase II | ||||||
Arm description |
Salvage treatment during phase II | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Brentuximab vedotin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1.8 mg/kg, IV, day 1
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Baseline characteristics reporting groups
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Reporting group title |
Phase II
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Reporting group description |
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End points reporting groups
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Reporting group title |
Salvage treatment during phase II
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Reporting group description |
Salvage treatment during phase II | ||
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End point title |
Metabolic CR rate (PET-CT) after the third cycle of BV-DHAP reinduction therapy [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
After the third cycle of BV-DHAP reinduction therapy
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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: There was no comparison between groups, only descriptive evaluation of metabolic CR rate, no direct comparison. The statistical analysis for an endpoint is thus not mandatory. This is why the statistical analysis was deleted (after consulting Sjennie Daelmans). |
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Attachments |
Final publication |
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| Notes [2] - 55 patients were included in the phase II part, 3 patients were not evaluable for response. |
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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 |
Adverse events of all grades regardless relationship to investigational product occurring from the the first study-related procedure until 30 days to end of treatment evaluation.
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Adverse event reporting additional description |
Adverse events occurring after 30 days should also be reported if considered at least possibly related
to the investigational medicinal product by the investigator.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Phase II
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Reporting group description |
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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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28 Sep 2015 |
1. The use of long-acting G-CSF (Neulasta) after the 1st and 3rd course of Brentuximab Vedotin + DHAP and after autologous stemcell transplantation is now obligatory to reduce the prolonged period of grade 4 granulocytopenia that was observed in the initial patients in the phase I part of the study who did not receive the growth factor : See section 5.2.2 and 5.4.3 in the protocol. NB. After course 2 all patients receive G-CSF in view of stem cell harvesting.
2. The definition of DLT has been extended : see section 5.2.3 , the Table in section 7.2 and section 17.7 in the protocol dealing with long-lasting granulocytopenia despite growth factor treatment after BV + DHAP.
3. Eligibility criteria for high dose BEAM chemotherapy followed by autologous stemcell transplantation have now been introduced in a new section in the protocol : 5.4.1.
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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/32273476 |
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