Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

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

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-11

Study Completion Date

2019-10-31

Brief Summary

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

This is a single-arm, open-label, multicenter study in approximately 52 adults with primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence) after treatment(s) including surgery and radiotherapy with or without chemotherapy and following discontinuation of any previous standard or investigational lines of therapy.

Related Clinical Trials

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

A Study of MEDI-575 in Subjects With Recurrent Glioblastoma Multiforme

NCT01268566

Glioblastoma Multiforme

COMPLETED PHASE2

Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma

NCT02208362

Recurrent Glioblastoma Recurrent Malignant Glioma Recurrent WHO Grade II Glioma +5 more

ACTIVE_NOT_RECRUITING PHASE1

Cediranib Maleate and Cilengitide in Treating Patients With Progressive or Recurrent Glioblastoma

NCT00979862

Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma +1 more

COMPLETED PHASE1

Carboxylesterase-Expressing Allogeneic Neural Stem Cells and Irinotecan Hydrochloride in Treating Patients With Recurrent High-Grade Gliomas

NCT02192359

Recurrent Anaplastic Astrocytoma Recurrent Anaplastic Oligoastrocytoma Recurrent Anaplastic Oligodendroglioma +4 more

ACTIVE_NOT_RECRUITING PHASE1

Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

NCT00662506

Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma

COMPLETED PHASE1/PHASE2

Detailed Description

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

The study drug, MDNA55, is a fusion protein comprising a genetically engineered Interleukin-4 (IL-4) linked to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE.

The study will be conducted at up to 10 clinical sites following institutional review board approval and completed informed consent.

Subjects that meet the study eligibility criteria will undergo surgery associated with study drug administration. MDNA55 will be administered locally by convection-enhanced delivery (CED).

Post-treatment follow-up assessment of safety and efficacy will be performed monthly for the first 6 months and bimonthly thereafter for approximately 1 year after study drug administrations. Subjects will continued to be followed for survival and post-study treatment(s) of GB after study completion or withdrawal.

Conditions

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

Glioblastoma Grade IV Astrocytoma Glioblastoma Multiforme Grade IV Glioma

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

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.

MDNA55

Single infusion of MDNA55 via convection enhanced delivery (CED).\*

\*Subjects may be eligible to receive a second administration of MDNA55.

Group Type EXPERIMENTAL

MDNA55

Intervention Type DRUG

MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Interventions

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

MDNA55

MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Intervention Type DRUG

Other Intervention Names

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

IL4-PE Interleukin-4 Pseudomonas Exotoxin Interleukin-4 Pseudomonas Toxin IL4 Pseudomonas Exotoxin NBI-3001 cpIL4-PE

Eligibility Criteria

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

Inclusion Criteria

1. Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks
2. Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence)
3. Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis
4. Recurrent tumor must be supratentorial, contrast-enhancing GB no smaller than 1 cm x 1 cm (largest perpendicular dimensions) and no larger than 4 cm maximum in a single direction based on MRI taken within 14 days prior to catheter placement
5. Karnofsky Performance Score (KPS) ≥ 70
6. Subjects must be able and willing to undergo multiple brain MRI examinations
7. Subjects must be able and willing to comply with all study procedures
8. Any related toxicities following discontinuation of prior GB therapies must have resolved to CTCAE Grade 1 or lower prior to inclusion in this study

Exclusion Criteria

1. Prior treatment with cytotoxic chemotherapy

1. Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion
2. "Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion
3. Nitrosoureas within the past 6 weeks prior to planned infusion
4. Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion
2. Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion
3. Prior treatment with bevacizumab (Avastin) or other vascular-endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors within the past 4 weeks prior to planned infusion
4. Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
5. Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion
6. Ongoing Optune© therapy within 5 days of planned infusion
7. Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA)
8. Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene.
9. Tumor in the brainstem (not including fluid-attenuated inversion recovery \[FLAIR\] changes), an infratentorial tumor, diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense tumor with ill-defined margins encompassing at least three lobes of the brain.
10. Tumor with a mass effect (e.g. 1-2 cm midline shift)
11. Subjects with tumors for which the preponderance of tissue is not of the type in which convection would be possible (e.g. preponderance of cystic component)
12. Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters
13. Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
14. Any condition that precludes the administration of anesthesia
15. Known to be human immunodeficiency virus positive
16. Concurrent or a history of any significant medical illnesses that in the Investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the subject's ability to tolerate the study drug therapy and/or put the subject at additional risk or interfere with the interpretation of the results of this trial
17. Known history of allergy to gadolinium contrast agents
18. Presence of another type of malignancy requiring treatment within \< 3 years prior to the screening visit, except for adequately treated carcinoma in-situ of the cervix, prostate cancer not actively treated, and basal or squamous cell carcinoma of the skin

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No