A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

NCT ID: NCT02026271

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2019-08-31

Brief Summary

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.

The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with oral veledimex.

Detailed Description

Eligible patients will be stratified to one of two groups, according to clinical indication for tumor resection. Patients who are scheduled for a standard of care craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days.

Patients not scheduled for tumor resection will receive Ad-RTS-hIL-12 by stereotactic injection and then will continue on oral veledimex for 14 days.

The study is divided into three periods: the screening period, the treatment period and the follow-up period.

Conditions

Glioblastoma Multiforme; Anaplastic Oligoastrocytoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ad-RTS-hIL-12+veledimex

varying doses of intratumoral Ad-RTS-hIL-12 (INXN-2001) and oral veledimex (activator ligand).

Group Type: EXPERIMENTAL

Ad-RTS-hIL-12

Intervention Type: BIOLOGICAL

• 2.0 x 10^11 viral particles (vp) per injection or 1.0 x 10^12 viral particles (vp) per injection
• one intratumoral injection of Ad-RTS-hIL-12

veledimex

Intervention Type: DRUG

• 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day)
• 14 oral daily doses of veledimex
• 1 Expansion cohort at a single dose level at or below MTD

Interventions

Ad-RTS-hIL-12

• 2.0 x 10^11 viral particles (vp) per injection or 1.0 x 10^12 viral particles (vp) per injection
• one intratumoral injection of Ad-RTS-hIL-12

Intervention Type: BIOLOGICAL

veledimex

• 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day)
• 14 oral daily doses of veledimex
• 1 Expansion cohort at a single dose level at or below MTD

Intervention Type: DRUG

Other Intervention Names

INXN-2001; INXN-1001; Activator Ligand

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects ≥ 18 and ≤ 75 years of age

2. Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection and treatment with investigational products prior to undergoing any study procedures

3. Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.

4. Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.

5. Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:

1. Nitrosoureas: 6 weeks

2. Other cytotoxic agents: 4 weeks

3. Anti-angiogenic agents including bevacizumab: 4 weeks

4. Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks

5. Experimental immunotherapies: 3 months

6. Vaccine based therapy: 3 months

6. Able to undergo standard MRI scans with contrast agent

7. Karnofsky Performance Status ≥ 70

8. Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:

1. Hemoglobin ≥ 9 g/L

2. Lymphocytes > 500/ mm3

3. Absolute Neutrophil Count ≥ 1500/ mm3

4. Platelets ≥ 100,000/ mm3

5. Serum creatinine ≤ 1.5 x ULN

6. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5 × ULN

7. Total bilirubin < 1.5 x ULN

8. International Normalized Ratio (INR) and activated Partial Thromboplastin Time [PTT] within normal institutional limits

9. Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria

1. Radiotherapy within 4 weeks or less prior to starting first veledimex dose

2. Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.

3. Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections

4. Use of systemic antibacterials, antifungals or antivirals for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is permitted perioperatively.

5. Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.

6. Other concurrent clinically active malignant disease, requiring treatment, with the exception of non-melanoma cancers of the skin or carcinoma in-situ of the cervix or non-metastatic prostate cancer.

7. Nursing or pregnant females

8. Prior exposure to veledimex

9. Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing

10. Presence of any contra-indication for a neurosurgical procedure

11. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator or medical monitor, jeopardize the safety of a subject and/or their compliance with the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alaunos Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaymes Holland

Role: STUDY_DIRECTOR

Alaunos Therapeutics

Locations

Cedars-Sinai

Los Angeles, California, United States

University of California - San Francisco

San Francisco, California, United States

Northwestern

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Brigham & Women's

Boston, Massachusetts, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Chiocca EA, Yu JS, Lukas RV, Solomon IH, Ligon KL, Nakashima H, Triggs DA, Reardon DA, Wen P, Stopa BM, Naik A, Rudnick J, Hu JL, Kumthekar P, Yamini B, Buck JY, Demars N, Barrett JA, Gelb AB, Zhou J, Lebel F, Cooper LJN. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019 Aug 14;11(505):eaaw5680. doi: 10.1126/scitranslmed.aaw5680.

Reference Type: DERIVED

PMID: 31413142 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ATI001-102

Identifier Type: -

Identifier Source: org_study_id