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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-27

Study Completion Date

2020-01-27

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Study in Patients With Primary Breast Diffuse Large B-cell Lymphoma

NCT01448096

Large B Cell Diffuse Lymphoma

COMPLETED PHASE2

Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma

NCT00290667

Lymphoma

COMPLETED PHASE2

Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.

NCT00355199

Diffuse Large B-Cell Lymphoma

COMPLETED PHASE3

Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma

NCT00052936

Lymphoma

COMPLETED PHASE3

Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma

NCT01856192

Ann Arbor Stage II Diffuse Large B-Cell Lymphoma Ann Arbor Stage III Diffuse Large B-Cell Lymphoma Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma

ACTIVE_NOT_RECRUITING PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

There are three planned analyses:

1. 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.
2. 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.
3. 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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lymphoma, Large B-Cell, Diffuse

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

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)

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

NGR-hTNF

Intervention Type DRUG

dose of 0.8 mcg/sqm

RITUXIMAB

Intervention Type OTHER

dose of 375 mg/mq

Doxorubicin

Intervention Type DRUG

dose of 50 mg/mq

Cyclophosphamide

Intervention Type DRUG

dose of 750 mg/mq

Vincristine

Intervention Type DRUG

dose of 1.4 mg/mq (max 2 mg)

Prednisone

Intervention Type DRUG

75 mg

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

NGR-hTNF

dose of 0.8 mcg/sqm

Intervention Type DRUG

RITUXIMAB

dose of 375 mg/mq

Intervention Type OTHER

Doxorubicin

dose of 50 mg/mq

Intervention Type DRUG

Cyclophosphamide

dose of 750 mg/mq

Intervention Type DRUG

Vincristine

dose of 1.4 mg/mq (max 2 mg)

Intervention Type DRUG

Prednisone

75 mg

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

mabthera adriamicina endoxan deltacortene

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Histological or cytological diagnosis of (D)LBCL
* Disease exclusively localized into the CNS (brain, meninges, cranial nerves, eyes and/or spinal cord) both at first diagnosis and failure
* Progressive or recurrent disease
* Previous treatment with high-dose-methotrexate-based chemotherapy ± WBRT
* Presence of at least one target lesion, bidimensionally measurable
* Age 18 - 80 years
* ECOG performance status 0-3
* Adequate bone marrow (platelets \>75.000/mm3, hemoglobin \>8 g/dl, ANC \>1.000/mm3), renal (serum creatinine \<2 times UNL and creatinine clearance ≥40 mL/min), cardiac (VEF ≥50%), and hepatic (SGOT/SGPT \<3 times UNL, bilirubin and alkaline phosphatase \<2 times UNL) function.
* Given written informed consent prior to any study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without any prejudice. Informed consent signed by a patient's guardian is acceptable if the patient is not able to decide inclusion in the study due to cognitive impairment

Exclusion Criteria

* Known HIV disease or other chronic immunodeficiency
* Patients with positive flow cytometry examination of the CSF, but negative results in CSF conventional cytology, and without any other evidence of CNS disease
* Patients with concomitant extra-CNS disease at presentation or relapse
* Symptomatic coronary artery disease, cardiac arrhythmias not well controlled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
* Any other serious medical condition which could impair the ability of the patient to participate in the trial
* Concurrent treatment with other antineoplastic drugs
* Therapy with PPI (Proton Pump Inhibitors, that may interfere with chromogranine levels, see above). For gastroprotective therapy H2-blockers (i.e. ranitidine) are allowed.
* Pregnant and lactating female patients. Sexually active patients of child bearing potential must implement adequate contraceptive measures during study participation.
* Previous or concurrent malignancies at other sites diagnosed or relapsed within the last 3 years of follow-up. Patients with surgically cured in situ carcinomas and basal cell carcinoma of the skin are allowed.
* Presence of any psycological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No