Clinical Trial Results:
A phase II study of SGN-35 (brentuximab vedotin) of patients with relapsed or refractory Primary mediastinal large B-cell lymphoma (PMLBCL).
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Summary
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EudraCT number |
2012-000735-27 |
Trial protocol |
IT |
Global end of trial date |
14 Jul 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Oct 2022
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First version publication date |
11 Oct 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_SGN01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02423291 | ||
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 |
Secretary, FONDAZIONE ITALIANA LINFOMI ONLUS, 0039 0131/033151, segreteriadirezione@filinf.it
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Scientific contact |
Secretary, FONDAZIONE ITALIANA LINFOMI ONLUS, 0039 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 |
17 Feb 2017
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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 |
14 Jul 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the antitumor efficacy of single-agent Brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in patients with relapsed or refractory primary mediastinal large B-cell lymphoma.
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Protection of trial subjects |
A patient’s treatment with Brentuximab vedotin may be discontinued for any of the following reasons:
• Disease progression.
• Stable disease or better and completed 16 treatment cycles.
• The Investigator or patient deems it in the patient’s best interest to discontinue. The reason justifying study treatment withdrawal must be documented in the CRF.
Patients who discontinue from study treatment will remain on study for follow-up unless they withdraw consent. All patients who receive at least 1 dose of study drug will be followed every 12 weeks until death or study closure, whichever comes first.
Intrapatient dose reduction to 1.2 mg/kg will be allowed depending on the type and severity of toxicity.
The start of the next cycle may be delayed for up to 3 weeks if additional time is required for the patient to recover from study treatment-associated toxicity experienced during the current cycle. Delays of greater than 3 weeks are prohibited without approval of the Sponsor.
Doses reduced for drug-related toxicity should generally not be re-escalated. However, intrapatient re-escalation to the previous dose level may be permitted at the discretion of the Investigator.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Oct 2013
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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: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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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) |
13
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Fifteen patients recruited in Italy from 2 October 2013 , with date of last completed at 8 October 2015. No screening failure, no waivers. The Sponsor and the Study Coordinator decided to stop the trial due to drug inefficacy on 14/Jul/2016 (last enrollment on 30/Jun/2015). | ||||||||||||
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Pre-assignment
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Screening details |
Study Population Eligible patients are those with relapsed or refractory primary mediastinal large B-cell lymphoma. 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 |
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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Single arm | ||||||||||||
Arm description |
This is a single-arm, open-label, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory PMLBCL who have previously received a first line of treatment with chemotherapy or immunotherapy. All treated patients will receive 1.8 mg/kg Brentuximab vedotin administered as a single outpatient IV infusion on Day 1 of each 21-day treatment cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better as assessed by investigator should receive a minimum of 8, but no more than 16 cycles of study treatment. | ||||||||||||
Arm type |
Single arm study | ||||||||||||
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 |
Powder for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Brentuximab vedotin, 1.8 mg/kg, administered via outpatient IV infusion on Day 1 of each 21-day cycle.
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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 |
This is a single-arm, open-label, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory PMLBCL who have previously received a first line of treatment with chemotherapy or immunotherapy. All treated patients will receive 1.8 mg/kg Brentuximab vedotin administered as a single outpatient IV infusion on Day 1 of each 21-day treatment cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better as assessed by investigator should receive a minimum of 8, but no more than 16 cycles of study treatment. | ||
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End point title |
Overall Objective Response Rate in Patients With Relapsed or Refractory PMLBCL [1] | ||||||||||||||||
End point description |
The antitumor efficacy of single-agent Brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in patients with relapsed or refractory primary mediastinal large B-cell lymphoma was determined using Cheson BD, Pfistner B, Juweid ME, et al. "Revised response criteria for malignant lymphoma". J Clin Oncol. 2007 Feb 10;25(5):579-586.Treatment response was assessed by dedicated spiral CT scan of neck, chest, neck, abdomen, and pelvis and PET scans performed at protocol-specified time points. Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment.
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End point type |
Primary
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End point timeframe |
42 months
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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: Trial was closed due to drug inefficacy on 14/Jul/2016 (last enrollment on 30/Jun/2015). |
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| Notes [2] - Trial was closed due to drug inefficacy on 14/Jul/2016 (last enrollment on 30/Jun/2015). |
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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 |
All Study Duration (3 years, 10 months)
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Adverse event reporting additional description |
We used the Common Terminology Criteria for Adverse Events v. 4.0 (CTCAE) for the coding of adverse events.
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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 |
Single arm
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Reporting group description |
This is a single-arm, open-label, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory PMLBCL who have previously received a first line of treatment with chemotherapy or immunotherapy. All treated patients will receive 1.8 mg/kg Brentuximab vedotin administered as a single outpatient IV infusion on Day 1 of each 21-day treatment cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better as assessed by investigator should receive a minimum of 8, but no more than 16 cycles of study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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03 Sep 2013 |
Seattle Genetics communication for the inclusion of a new side effect in the Information for patients enrolled in protocols with Brentuximab Vedotin (SGN-35) |
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22 Jun 2014 |
Variation of the Coordinator Investigator Dr. Vittorio Stefoni instead of Prof. Pier Luigi Zinzani; updating of parts relating to toxicity and relative modification of drug doses, new pharmaceutical company pharmacovigilance contacts, correction of marginal typos to the protocol, updating of the list of centers, changes to the contract based on requests from the CE of Reggio Emilia and Bologna. |
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30 Oct 2014 |
Notice from Millennium Takeda regarding the transition of the drug Adcetris® Brentuximab Vedotin (SGN-35) from experimental to commercial for experimental use. ONLY FOR AIFA AND COORDINATOR |
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03 Sep 2015 |
New IB, new FIL / Millennium contract, new consents. |
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19 Feb 2016 |
New IB and related changes to consents. |
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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 | |||||||
