NCT03536039: INGRID

RCHOP Chemoimmunotherapy Preceded BY BBB Permeabilization by t-NGR Necrosis Factor

Completed Phase 2 Last updated 3 August 2022

What this trial tests

Phase 2 trial testing NGR-hTNF in Lymphoma, Large B-Cell, Diffuse in 28 participants. Completed in 27 January 2020.

Timeline

27 January 2016

Primary endpoint
27 January 2019

27 January 2020

Quick facts

Lead sponsor	Andres J. M. Ferreri
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	28
Start date	27 January 2016
Primary completion	27 January 2019
Estimated completion	27 January 2020
Sites	1 location across Italy

Drugs / interventions tested

• NGR-hTNF
• RITUXIMAB — full drug profile →
• Doxorubicin
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Vincristine (vincristine) — full drug profile →
• Prednisone (prednisone) — full drug profile →

Conditions studied

• Lymphoma, Large B-Cell, Diffuse — all drugs for Lymphoma, Large B-Cell, Diffuse →

Sponsor

Andres J. M. Ferreri — full company profile →

Who can join

Adults 18 to 80, any sex, with Lymphoma, Large B-Cell, Diffuse. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose-methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. Treatment with R-CHOP, the most commonly used combination against aggressive lymphomas, could overcome these difficulties, but CNS bioavailability of related drugs is poor due to their limited capability to cross the blood-brain barrier (BBB). Tumor necrosis factor (TNF) induces selective BBB permeabilization and enhances CNS access of anticancer drugs in animal models. The addition of NGR peptide improves biological properties of TNF, resulting in increased drug availability and antitumor synergistic effect, without increased toxicity. Thus, the addition of NGR-hTNF to R-CHOP may result in improved CNS drug availability and activity in patients with relapsed/refractory PCNSL; this hypothesis is being tested in this ongoing phase II trial called "INGRID". This trial will consider HIV-negative patients (age 18-80 ys; ECOG PS ≤3) with relapsed/refractory PCNSL previously treated with high-dose-methotrexate-based chemotherapy± radiotherapy, and with measurable disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy.
   Upton DH, Ung C, George SM, Tsoli M, et al · · 2022 · cited 96× · PMID 35832071 · DOI 10.7150/thno.69682
2. Introduction of novel agents in the treatment of primary CNS lymphoma.
   Grommes C, Nayak L, Tun HW, Batchelor TT. · · 2019 · cited 61× · PMID 30423172 · DOI 10.1093/neuonc/noy193
3. R-CHOP preceded by blood-brain barrier permeabilization with engineered tumor necrosis factor-α in primary CNS lymphoma.
   Ferreri AJM, Calimeri T, Conte GM, Cattaneo D, et al · · 2019 · cited 43× · PMID 31118164 · DOI 10.1182/blood.2019000633
4. Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy.
   Wang T, Suita Y, Miriyala S, Dean J, et al · · 2021 · cited 33× · PMID 33918635 · DOI 10.3390/pharmaceutics13040520
5. Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial.
   Ferreri AJM, Calimeri T, Ponzoni M, Curnis F, et al · · 2020 · cited 26× · PMID 32766857 · DOI 10.1182/bloodadvances.2020002270
6. Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?
   Verhulst E, Garnier D, De Meester I, Bauvois B. · · 2022 · cited 19× · PMID 35158891 · DOI 10.3390/cancers14030624
7. 10th European Conference on Rare Diseases & Orphan Products (ECRD 2020).
   · 2020 · cited 3× · PMID 33168048 · DOI 10.1186/s13023-020-01550-1
8. 47° Congress of the Italian Society of Hematology Rome, Italy, October 7-9, 2019
   · 2019