Clinical Trial Results:
MONO-INSTITUTIONAL PHASE II TRIAL ADDRESSING TOLERABILITY AND ACTIVITY OF R-CHOP CHEMOIMMUNOTHERAPY PRECEDED BY BLOOD-BRAIN BARRIER PERMEABILIZATION BY NGR-TUMOR NECROSIS FACTOR IN PATIENTS WITH RELAPSED OR REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
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Summary
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EudraCT number |
2014-001532-11 |
Trial protocol |
IT |
Global end of trial date |
24 Dec 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Feb 2026
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First version publication date |
12 Feb 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 |
Ingrid
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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 Ospedale San Raffaele
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Sponsor organisation address |
Via Olgettina 60, Milan, Italy,
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Public contact |
Lymphoid malingnancies Unit Data Ma, Ospedale San Raffaele, +39 0226433919, ferreri.andres@hsr.it
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Scientific contact |
Lymphoid malingnancies Unit Data Ma, Ospedale San Raffaele, +39 0226433919, 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 |
03 Aug 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Aug 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
24 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 |
feasibility of chemo-immunotherapy with standard R-CHOP preceded by Ngr-TNF
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Protection of trial subjects |
Common protection due to Clinical Trial partecipant:
- Pharmacovigilance
- Ethical Supervision
- Clincial peer reviewing
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jan 2016
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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: 28
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Worldwide total number of subjects |
28
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EEA total number of subjects |
28
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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) |
23
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
- | ||||||
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Pre-assignment period milestones
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Number of subjects started |
28 | ||||||
Number of subjects completed |
28 | ||||||
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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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Treatment | ||||||
Arm description |
Outpatient (inpatient only if clinically indicated) Patients will receive NGR-hTNF at dose of 0.8 mcg/sqm 1 hour before standard R-CHOP (cyclophosphamide-doxorubicin-vincristine-prednisone-rituximab) regimen every 3 weeks for six courses Day 1: Rituximab 375 mg/m2 as IV infusion NGR-hTNF 0.8 μg/m2 as 1-hour infusion Cyclophosphamide 750 mg/m2 as IV bolus Doxorubicin 50 mg/m2 as IV bolus Vincristine 1.4 mg/m2 (max. 2 mg) as IV bolus Days 2-6: Prednisone 75 mg/d oral Any kind of consolidation treatment is allowed (i.e. WBRT, ASCT, maintenance using alkylating agents or oral immunodulatory drugs) | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
NGR-hTNF
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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 |
Injection
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Dosage and administration details |
dose of 0.8 mcg/sqm 1 hour before standard R-CHOP
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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 |
Treatment
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Reporting group description |
Outpatient (inpatient only if clinically indicated) Patients will receive NGR-hTNF at dose of 0.8 mcg/sqm 1 hour before standard R-CHOP (cyclophosphamide-doxorubicin-vincristine-prednisone-rituximab) regimen every 3 weeks for six courses Day 1: Rituximab 375 mg/m2 as IV infusion NGR-hTNF 0.8 μg/m2 as 1-hour infusion Cyclophosphamide 750 mg/m2 as IV bolus Doxorubicin 50 mg/m2 as IV bolus Vincristine 1.4 mg/m2 (max. 2 mg) as IV bolus Days 2-6: Prednisone 75 mg/d oral Any kind of consolidation treatment is allowed (i.e. WBRT, ASCT, maintenance using alkylating agents or oral immunodulatory drugs) | ||
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End point title |
ORR complete and partial responses based on IPCG response criteria [1] | ||||||||
End point description |
Overall response rate (ORR), defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to the IPCG response criteria, assessed at the end of treatment after completion of 6 cycles of R-CHOP chemo-immunotherapy preceded by NGR-hTNF and prior to any consolidative therapy.
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End point type |
Primary
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End point timeframe |
ORR was evaluated after completion of 6 cycles of R-CHOP, before any consolidative 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: This is a single-arm, descriptive study. The two-stage Simon Minimax design will be used. The maximum overall response rate (complete and partial responses) considered of low interest will be 30% [17], and the minimum response rate considered of interest will be 50%; to demonstrate that difference, a total of 28 patients will be needed (one-sided test; type I error .10; power .9). No formal statistical comparison with a control group will be performed. |
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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 inclusion until 30 days after end of treatment
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Adverse event reporting additional description |
Patients will be instructed by the investigator to report the occurrence of any AE. The investigator assesses and records all AEs observed during the AE reporting period.
AEs are coded with the NCI Common Terminology Criteria for Adverse Event
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-NCIC CTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
3
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Reporting groups
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Reporting group title |
Adverse event
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Reporting group description |
There were no cases of unexpected toxicity or interruptions because of toxicity, and no patient needed a reduction in dose of either NGR-hTNF or R-CHOP. Only 6 courses (4%) were delayed (cytopenia). Sixteen serious AEs were recorded in 12 patients: grade 1 to 2 seizures (3), grade 1 to 2 deep venous thrombosis (2), grade 3 infections (5), grade 3 syncope (2), grade 3 constipation, grade 4 febrile neutropenia, pulmonary aspergillosis, and grade 2 left ventricular function reduction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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/32766857 |
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