MSC-DNX-2401 in Treating Patients With Recurrent High-Grade Glioma

Recurrent Glioblastoma Clinical Trial

Official title: Phase I Clinical Trial of Allogeneic Bone Marrow Human Mesenchymal Stem Cells Loaded With A Tumor Selective Oncolytic Adenovirus, DNX-2401, Administered Via Intra-Arterial Injection in Patients With Recurrent High-Grade Glioma

Status Recruiting

Clinical Trial Summary

This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent glioblastoma (GBM), IDH-mutant astrocytoma grade 4, gliosarcoma, or wild-type IDH-1 anaplastic astrocytoma.

II. To determine the local and systemic toxicity of allogeneic BM-hMSCs-DNX2401 administered by intra-arterial injection (i.e., transfemoral endovascular intracranial injection) in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

III. To determine at the molecular and cellular level the capacity of allogeneic BM-hMSCs-DNX2401 administered intra-arterially to home to and deliver DNX-2401 to recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma by analyzing post-treatment surgical brain tumor specimens for the expression and distribution of adenoviral proteins.

SECONDARY OBJECTIVES:

I. To assess shedding of adenovirus into the blood, sputum, and nasopharynx after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

II. To assess the development of anti-adenovirus antibodies after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

III. To evaluate immune-mediated cytokine responses after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

IV. To assess anti-tumoral activity and to determine progression-free survival (PFS) and overall survival (OS) after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

OUTLINE: This is a dose-escalation study.

PART I: Patients receive one or two infusions of BM-hMSCs-DNX-2401 intra-arterially (IA) over 20-30 minutes on day 0. Dose level 1-5 will receive 1 infusion. Dose level 6 will receive 2 infusions.

PART II: Patients receive one or two infusions BM-hMSCs-DNX-2401 IA, depending on the highest dose that was tolerated in Part 1. After 2 weeks, patients undergo surgery where the tumor is removed, then receive intramural injection of BM-hMSCs-DNX-2401 into the resection cavity.

After completion of study treatment, patients in both part I and II are followed up on days 1, 4, 7, and 14 of month 1,every 6 weeks for 6 months (4 visits), then every 8 weeks for 1 year (6 visits), then every 4 months for 1 year (3 visits), then every 6 months until the tumor grows back. Patients treated at Dose level 6 in Part 1 and Part 2 are also followed up on Day 12, then on Day 1, 4, and 7 after second infusion, then on Day 1, 7, and 14 post-craniotomy for Part 2, Dose Level 6, then ,every 6 weeks for 6 months (4 visits), then every 8 weeks for 1 year (6 visits), then every 4 months for 1 year (3 visits), then every 6 months until the tumor grows back. ;

Related Conditions & MeSH terms

• Astrocytoma
• Glioblastoma
• Glioma
• Gliosarcoma
• IDH1 wt Allele
• Recurrence
• Recurrent Anaplastic Astrocytoma
• Recurrent Glioblastoma
• Recurrent Gliosarcoma
• Recurrent Malignant Glioma

• NCT number: NCT03896568
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Frederick Lang
• Phone: 713-792-2400
• Email: flang@mdanderson.org
• Status: Recruiting
• Phase: Phase 1
• Start date: February 12, 2019
• Completion date: September 30, 2027