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

NCT03896568 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2015-0953NCI-2019-01195
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

IDH1 wt Allele; Recurrent Anaplastic Astrocytoma; Recurrent Glioblastoma; Recurrent Gliosarcoma; Recurrent Malignant Glioma

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose (MTD)

  The MTD will be defined as the dose below the dose that results in greater than or equal to one-third of the subjects exposed who experienced grade 3 or 4 (except hematological, grade 4 required) toxicity according to National Cancer Institute Common Toxicity Criteria that is deemed to be at least "probably related" to the study drug (i.e., dose-limiting toxicity \[DLT\]).

  Up to 28 days

• Incidence of adverse events (AEs)

  AEs will be summarized both overall and by dose group and tabulated by severity, relationship to BM-hMSCs-DNX 2401and causality. The number and percentage of subjects experiencing AEs will be tabulated by body system/preferred term both overall and by dose group. When an AE occurs more than once, the maximum severity and causality will be counted.

  Up to 1 year

Secondary Outcomes (5)

• Tumor response

  Up to 1 year

• Time to progression

  Up to 1 year

• Virus replication in tumor

  Up to 1 year

• Virus shedding

  Up to 1 year

• Immunogenicity based on adenoviral (AdV) antibodies

  Up to 1 year

Study Arms (2)

Part I (oncolytic adenovirus Ad5-DNX-2401)

EXPERIMENTAL

Patients receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes on day 0.

Biological: Oncolytic Adenovirus Ad5-DNX-2401

Part II (oncolytic adenovirus Ad5-DNX-2401, surgery)

EXPERIMENTAL

Patients receive oncolytic adenovirus Ad5-DNX-2401 as in part I. After 2 weeks, patients undergo surgery, then receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes.

Biological: Oncolytic Adenovirus Ad5-DNX-2401; Procedure: Therapeutic Conventional Surgery

Interventions

Oncolytic Adenovirus Ad5-DNX-2401 BIOLOGICAL

Given IA

Also known as: Ad5-Delta24RGD, DNX-2401, DNX2401, Oncolytic Ad5-Delta 24RGD, Oncolytic Adenovirus Ad5-Delta 24RGD

Part I (oncolytic adenovirus Ad5-DNX-2401); Part II (oncolytic adenovirus Ad5-DNX-2401, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Part II (oncolytic adenovirus Ad5-DNX-2401, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments, and adhere to the protocol schedule.
• Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence.
• Male or female patients ≥ 18 years of age.
• Patients must be able to undergo endovascular treatment based on Doppler studies showing ICA that is less than 50% occluded.
• For patients undergoing resection for biological endpoints, tumors must be surgically resectable at the time of baseline evaluation and craniotomy for tumor resection is indicated as part of their standard medical care.
• Tumors must be ≥1.0 cm in diameter with upper limit of 5 cm maximal diameter.
• Patients must have a Karnofsky performance score ≥ 70.
• Patients must have a life expectancy of at least 16 weeks.
• Patients must have adequate bone marrow function (absolute granulocyte count \> 1,500 and platelet count of \> 75,000), adequate liver function (SGPT and SGOT and bilirubin \< 2 times institutional normal ranges), and adequate renal function (creatinine \< 2.0 times institutional normal) prior to starting therapy.
• Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) ≤ 1.5x ULN.
• Subjects who have received the following chemotherapies must have completed them within the following time periods prior to Baseline/Day 0 of hMSC-DNX2401 delivery with recovery from any drug-related toxic effects to Grade 1, or less, severity:
• Four weeks from cytotoxic agents (3 weeks from procarbazine or Temozolomide, 2 weeks from vincristine)
• weeks from nitrosoureas (CCNU, BCNU)
• Four weeks from any targeted investigational agent
• One week from non-cytotoxic agents

You may not qualify if:

• Histology other than GBM, gliosarcoma, IDH wild-type astrocytoma grade III or IDH-mutant astrocytoma grade 4.
• Tumor foci detected below the tentorium or beyond the cranial vault.
• Tumor within the posterior fossa.
• Tumor with leptomeningeal spread.
• Difficulty in obtaining vascular access for percutaneous procedure.
• Ipsilateral carotid stenosis (\>50%, by Doppler studies).
• Thrombophilias or primary hematological diseases.
• Transfusions or medications (G-CSF) to treat pancytopenia or other hematological conditions \< 28 days prior to Baseline/Day 0/hMSC-DNX2401 administration.
• Biologic/immunotherapy within 2 weeks of baseline.
• Clinical or laboratory evidence of inflammatory and/or autoimmune disorders.
• Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc. In addition, subjects must present with tumor that is evaluable by MRI.
• Pregnant or nursing females.
• Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. All subjects must be afebrile (i.e., \<38.0° Celsius \[C\]).
• Any medical condition that precludes surgery or endovascular treatment
• Alcoholism (dependency), alcohol or substance abuse within twelve (12) months prior to screening that has caused health consequences.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• DNAtrix, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Chen SR, Chen MM, Ene C, Lang FF, Kan P. Perfusion-guided endovascular super-selective intra-arterial infusion for treatment of malignant brain tumors. J Neurointerv Surg. 2022 Jun;14(6):533-538. doi: 10.1136/neurintsurg-2021-018190. Epub 2021 Nov 25.

  PMID: 34824133 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Gliosarcoma; Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Frederick F Lang

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frederick Lang

CONTACT

713-792-2400; flang@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 1, 2019
• Study Start: February 12, 2019
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)