RCHOP Chemoimmunotherapy Preceded BY BBB Permeabilization by t-NGR Necrosis Factor (INGRID)
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|ClinicalTrials.gov Identifier: NCT03536039|
Recruitment Status : Unknown
Verified May 2018 by Andres J. M. Ferreri, IRCCS San Raffaele.
Recruitment status was: Recruiting
First Posted : May 24, 2018
Last Update Posted : May 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma, Large B-Cell, Diffuse||Drug: NGR-hTNF Other: RITUXIMAB Drug: Doxorubicin Drug: Cyclophosphamide Drug: Vincristine Drug: Prednisone||Phase 2|
There are three planned analyses:
- An exploratory analysis (proof of principle) on the first 10 enrolled patients. In the case the experimental treatment will be safe and some tumor responses will be recorded, the chairman, after due multidisciplinary discussion, could propose to proceed with an open, non-comparative phase II trial, with overall response rate (complete and partial responses) as primary endpoint. The maximum overall response rate considered of low interest will be 30%, 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; trype I error .10; power .9). Importantly, BBB permeabilization will be investigated using different methods. Variations in tumor microvasculature and vessel permeability will be assessed by DCE- and DSC-MRI. Permeability will be assessed in contrast-enhanced lesions, perilesional areas and normal appearing brain; results will expressed as KTRANS values normalized using contralateral normal appearing white matter, and compared by Wilcoxon Signed Rank Test. Concentrations of R-CHOP drugs were assessed on matched CSF and serum/plasma samples.Moreover, BBB permeability will be also assessed by 99mTc-diethylene-triamine-pentacetic acid (99mTc-DTPA) brain scintigraphy.
- First of the two stages of Simon Minimax design, where 12 patients will be entered (including the 10 patients of the exploratory phase) and, if at least 4 responses will be observed, the study will be continued until a total of 28 patients will be entered.
- Second stage of Simon Minimax design: final analysis of activity on the whole series (n=28); the experimental treatment will be declared active if at least 12 responses will be observed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||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 (except for course #1 in which only standard R-CHOP regimen will be administered)|
|Masking:||None (Open Label)|
|Official Title:||Monoinstitutional Phase II Trial Addressing Tolerability and Activity of RCHOP Chemoimmunotherapy Preceded by BBB Permeabilization by t-NGR Necrosis Factor in Patients With Relapsed/Refractory Primary Central Nervous System Lymphoma|
|Actual Study Start Date :||January 27, 2016|
|Estimated Primary Completion Date :||January 27, 2019|
|Estimated Study Completion Date :||January 27, 2020|
Experimental: NGR-hTNF + R-CHOP
Treatment includes one course of conventional R-CHOP followed by 5 courses of conventional R-CHOP (rituximab, Cyclophosphamide, vincristine, doxorubicin, prednisone) in conjunction with intravenous delivery of NGR-hTNF. Chemoimmunotherapy courses will be delivered every 3 weeks; day 22 is to be considered as day 1 of the subsequent course
dose of 0.8 mcg/sqm
dose of 375 mg/mq
Other Name: mabthera
dose of 50 mg/mq
Other Name: adriamicina
dose of 750 mg/mq
Other Name: endoxan
dose of 1.4 mg/mq (max 2 mg)
Other Name: deltacortene
- ORR: CR and PR based on IPCG response criteria [ Time Frame: up to 18 weeks ]Activity in terms of overall response rate (ORR): Complete Response (CR) and Partial Response (PR) of R-CHOP21 chemo-immunotherapy preceded by BBBP by NGR-hTNF.
- Duration of Response (DOR) [ Time Frame: 18 months ]DOR will be assessed for all responsive patients; time to documentation of tumor response to failure
- Progression-free survival (PFS) [ Time Frame: 12 months ]PFS will be assessed for all treated patients; it is defined as the interval between the time of entry onto trial and failure (relapsing or progressive disease), death from any cause or date of the last visit of follow-up
- Overall survival (OS) [ Time Frame: 12 months ]OS will be assessed for all enrolled patients; it is defined as the time from entry onto trial until death from any cause or date of the last visit of follow-up.
- Tolerability: defined by of grade 3-4 AEs according to NCI CTCAE. [ Time Frame: 12 months ]Tolerability will be assessed for all enrolled patients; it is defined by of grade 3-4 AEs according to NCI CTCAE.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03536039
|Contact: Andrés Jose Maria Ferreri, MDemail@example.com|
|Contact: Teresa Calimeri, MDfirstname.lastname@example.org|
|Principal Investigator:||Andrés Jose Maria Ferreri, MD||San raffaele hospital|