Clinical Trial Results:
Multicenter European pilot study of 90Yttrium-ibritumomab tiuxetan as first line therapy for stage III – IV follicular lymphoma (and selected patients with extended stage II) followed by consolidation Rituximab for patients in complete remission but with persistent molecular disease
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Summary
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EudraCT number |
2006-005778-34 |
Trial protocol |
DE SE AT |
Global end of trial date |
30 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2022
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First version publication date |
15 Dec 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 |
Zevalin first line in FL
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00772655 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Charité - University Hospital of Berlin
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Sponsor organisation address |
Hindenburgdamm 30, Berlin, Germany, 12200
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Public contact |
Antonio Pezzutto, Department of Hematology, Oncology and Tumor Immunology,CBF, +49 30 450 513631, antonio.pezzutto@charite.de
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Scientific contact |
Antonio Pezzutto, Department of Hematology, Oncology and Tumor Immunology,CBF, +49 30 450 513631, antonio.pezzutto@charite.de
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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 |
30 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Jun 2010
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jun 2015
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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 end point of this prospective, nonrandomized phase II trial is the clinical and molecular remission rate in response to 90Y-ibritumomab tiuxetan.
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Protection of trial subjects |
Because of safety concerns at the time of protocol writing, the local radiation safety authority suggested limiting recruitment to patients age 50 years or older. Eligible patients had to have untreated, histologically confirmed, CD20FL grade 1 to 3a,10 stage II, III, or IV, bidimensionally measurable disease. In case of stage II, only patients requiring extensive radiation fields were eligible. For treatment, at least one of the following was required: presence of “B” symptoms, tumor progression more than 50% in 6 months, organ compression by tumor, bulky disease (lesions5 cm on at least one axis) or grade 3a FL. Patients were not eligible in case of bone marrow infiltration more than 25%, leukocytopenia less than 2,500/L, thrombocytopenia less than 100,000/µL, bulky disease exceeding 10 cm in the largest diameter, CNS lymphoma manifestation, circulating tumor cells more than 500/µL, pleural effusion, or ascites above 1,000 mL.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
14 Jun 2007
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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 |
Sweden: 8
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Country: Number of subjects enrolled |
Austria: 9
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Country: Number of subjects enrolled |
Germany: 25
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Country: Number of subjects enrolled |
Italy: 17
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Worldwide total number of subjects |
59
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EEA total number of subjects |
59
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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) |
26
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From 65 to 84 years |
33
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85 years and over |
0
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Recruitment
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Recruitment details |
Between June 2007 and June 2010, 35 females and 24 males were included in the trial | ||||||
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Pre-assignment
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Screening details |
72 Patients were screened 13 patients were exluded due to criteria 59 were randomized | ||||||
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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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90YIT RIT - Group | ||||||
Arm description |
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Arm type |
Experimental | ||||||
Investigational medicinal product name |
90Yttrium-Ibritumomab tiuxetan
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Investigational medicinal product code |
Therapeutic Radiopharmaceutical
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients received rituximab 250 mg/m2 on day 1 followed by 185 MBq indium for dosimetry. On day 8 or 9, patients were given a second infusion of rituximab 250mg/m2 followed by 15 MBq/kg 90YIT up to amaximumdose
of 1,200 MBq.
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Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
Antineoplastic agents, Monoclonal antibodies
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients received rituximab 250 mg/m2 on day 1 followed by 185 MBq 111indium for dosimetry. On day 8 or 9, patients were given a second infusion of rituximab 250mg/m2 followed by 15 MBq/kg 90YIT up to amaximumdose of 1,200 MBq.
Patients who attained clinical CR but had evidence of molecular MRD received a consolidation treatment with rituximab 375 mg/m2 once per week for 4 weeks followed by four courses of rituximab 375 mg/m2 given at 8-week intervals.
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Baseline characteristics reporting groups
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Reporting group title |
90YIT RIT - Group
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
90YIT RIT - Group
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Reporting group description |
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Subject analysis set title |
Molecular Response Group
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
CR(u), (unconfirmed) complete response;
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End point title |
Response After Therapy With 90YIT | ||||||||||||||||||||||||||||||
End point description |
CR, complete response; CRu, unconfirmed complete response;
PD, progressive disease; PR, partial response; SD, stable disease
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End point type |
Primary
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End point timeframe |
at 6 Months
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Statistical analysis title |
Change of the clinical and molecular Reponse | ||||||||||||||||||||||||||||||
Comparison groups |
90YIT RIT - Group v Molecular Response Group
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Toxicity grade 3 | ||||||||||||||||
End point description |
Hematologic
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End point type |
Secondary
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End point timeframe |
12 months after 90Yttriumibritumomab- tiuxetan (90YIT)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Toxicity Grade 4 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 months after 90YIT
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Toxicity Grade 2 | ||||||||||||||||||||
End point description |
Nonhematologic toxicities never reached grade 3 or 4. Grade 2 toxicities included infections, gastrointestinal and cardiovascular adverse
events, and skin irritations and mucositis.
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End point type |
Secondary
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End point timeframe |
12 months after 90YIT
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
PFS | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After a median follow-up of 30.6 months
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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 |
12 months
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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 |
8.1
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Reporting groups
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Reporting group title |
90YIT RIT - Group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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09 Feb 2009 |
Request for prolongation of the recruitment period of the study until 30.06.2010. Change of co-PI |
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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/2323371 |
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