GlioblastomaPhase 2NCT02858895

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

A Phase 2 study testing MDNA55 in people with Glioblastoma and Grade IV Astrocytoma, run by Medicenna Therapeutics, Inc. at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma, Grade IV Astrocytoma, Glioblastoma Multiforme
What is being tested?: MDNA55
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 7 sitesUnited States
Study dates: 11 Apr 2017to 31 Oct 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks
Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence)
Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis
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
Karnofsky Performance Score (KPS) ≥ 70
Subjects must be able and willing to undergo multiple brain MRI examinations
Subjects must be able and willing to comply with all study procedures
Any related toxicities following discontinuation of prior GB therapies must have resolved to CTCAE Grade 1 or lower prior to inclusion in this study

Who cannot join

Prior treatment with cytotoxic chemotherapy
Temozolomide (standard induction and / or maintenance dosing) within the past 4 weeks prior to planned infusion
"Metronomic" Temozolomide (low-dose, continuous administration) within the past 7 days prior to planned infusion
Nitrosoureas within the past 6 weeks prior to planned infusion
Treatment with any other cytotoxic agent within the past 4 weeks prior to planned infusion
Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion

Show all 22Show fewer

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
Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion
Ongoing Optune© therapy within 5 days of planned infusion
Secondary GB (i.e., GB that progressed from low-grade diffuse astrocytoma or AA)
Known mutation in either the isocitrate dehydrogenase 1 (IDH1) or the IDH2 gene.
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.
Tumor with a mass effect (e.g. 1-2 cm midline shift)
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)
Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters
Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
Any condition that precludes the administration of anesthesia
Known to be human immunodeficiency virus positive
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
Known history of allergy to gadolinium contrast agents
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

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Boca Raton Regional Hospital
Boca Raton, Florida, 33486
Duke University Medical Center
Durham, North Carolina, 27710
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19107
Oregon Health & Science University
Portland, Oregon, 97239
Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
University of California San Francisco
San Francisco, California, 94143
John Wayne Cancer Institute at Providence Saint John's Health Center
Santa Monica, California, 90404

Other trials in United States

About this study

Official title: An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

Read the detailed description

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: Glioblastoma, Grade IV Astrocytoma, Glioblastoma Multiforme, Grade IV Glioma
Being tested: MDNA55
Keywords: High grade glioma, malignant glioma, recurrent glioblastoma, recurrent GBM, recurrent GB, glioblastoma (GB), glioblastoma multiforme (GBM), progressive glioblastoma, Brain tumor, Brain cancer, immunotherapy, targeted, IL4R
Medical subject headings: Glioblastoma, Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MDNA55Drug
Also called IL4-PE, Interleukin-4 Pseudomonas Exotoxin, Interleukin-4 Pseudomonas Toxin, IL4 Pseudomonas Exotoxin
MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).

Study groups in NCT02858895
Study group	Role	What they receive
MDNA55	Experimental	Single infusion of MDNA55 via convection enhanced delivery (CED).* *Subjects may be eligible to receive a second administration of MDNA55. Receives: Drug: MDNA55

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival (OS)
Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.
Measured: From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.

Secondary outcomes (2)

Objective Response Rate (ORR)
ORR, determined by independent central review (per RANO-based criteria) Complete Response - Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks.
Partial Response - ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks Progressive Disease - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions.
Stable Disease - Does not qualify for CR, PR, or PD as defined above
Measured: 12 months
Progression Free Survival (PFS)
PFS, time from treatment until disease progression (per RANO-based criteria) or death Progressive Disease per RANO - At least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Apr 201731 Oct 2019

First posted8 Aug 2016 (estimated)
Study start11 Apr 2017
Primary completion12 Sep 2019
Study completion31 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for GlioblastomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02858895
Sponsor's protocol ID: MDNA55-05
Status last verified: Oct 2022
First submitted: 28 Jul 2016
Last updated: 24 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Sampson JH, Singh Achrol A, Aghi MK, Bankiewicz K, Bexon M, Brem S, Brenner A, Chandhasin C, Chowdhary S, Coello M, Ellingson BM, Floyd JR, Han S, Kesari S, Mardor Y, Merchant F, Merchant N, Randazzo D, Vogelbaum M, Vrionis F, Wembacher-Schroeder E, Zabek M, Butowski N. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial. Neuro Oncol. 2023 Jun 2;25(6):1085-1097. doi: 10.1093/neuonc/noac285.
PubMed 36640127
Ellingson BM, Sampson J, Achrol AS, Aghi MK, Bankiewicz K, Wang C, Bexon M, Brem S, Brenner A, Chowdhary S, Floyd JR, Han S, Kesari S, Randazzo D, Vogelbaum MA, Vrionis F, Zabek M, Butowski N, Coello M, Merchant N, Merchant F. Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma. Clin Cancer Res. 2021 Jul 15;27(14):3916-3925. doi: 10.1158/1078-0432.CCR-21-0446. Epub 2021 Apr 16.
PubMed 33863808

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma
ClinicalTrials.gov ID: NCT02858895
Acronym / sponsor ID: MDNA55-05
Conditions: Glioblastoma, Grade IV Astrocytoma, Glioblastoma Multiforme, Grade IV Glioma
Keywords: High grade glioma, malignant glioma, recurrent glioblastoma, recurrent GBM, recurrent GB, glioblastoma (GB), glioblastoma multiforme (GBM), progressive glioblastoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Medicenna Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 11 Apr 2017 (actual)
Primary completion: 12 Sep 2019 (actual)
Study completion: 31 Oct 2019 (actual)
First posted: 8 Aug 2016 (estimated)
Results: Posted 24 Oct 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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).

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
MDNA55	Experimental	Drug: MDNA55Single infusion of MDNA55 via convection enhanced delivery (CED).* *Subjects may be eligible to receive a second administration of MDNA55.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Subjects must be ≥ 18 years old and have a life expectancy ≥ 12 weeks
Histologically proven, primary (de novo) GB that has recurred or progressed (first or second recurrence, including this recurrence)
Confirmation that archived tissue is available from first diagnosis of GB for biomarker analysis
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
Karnofsky Performance Score (KPS) ≥ 70

Key exclusion criteria (22 listed)

Prior treatment with cytotoxic chemotherapy
Prior investigational treatment within the past 4 weeks or prior immunotherapy or antibody therapy within the past 4 weeks prior to planned infusion
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
Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) within the past 12 weeks prior to planned infusion
Prior surgery (including stereotactic radiosurgery and biopsy procedures) within the past 4 weeks prior to planned infusion

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MDNA55Also: IL4-PE, Interleukin-4 Pseudomonas Exotoxin, Interleukin-4 Pseudomonas Toxin, IL4 Pseudomonas ExotoxinMDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).	Drug	MDNA55

Primary outcome

Overall Survival (OS)
Time frame: From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.
Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies versus the alternative hypothesis of 11.5 months.

2 secondary outcomes

Objective Response Rate (ORR)
Time frame: 12 months
Progression Free Survival (PFS)
Time frame: 12 months

Results and safety

Results posted to the registry on 24 Oct 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MDNA55	47	8

Primary outcome: Overall Survival (OS)

Time frame: From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.. Median (80% Confidence Interval). Unit: months

Measure	MDNA55 (ITT Analysis) n = 47	MDNA55 (PP Analysis) n = 44
Value	10.2 (8.39 to 12.75)	11.64 (8.62 to 15.02)

Population analysed: Primary endpoint analysis was based on the ITT population. The null hypothesis was mOS of 8.0 months, based on a clinically-weighted average of published studies of FDA-approved therapies. ITT/Safety population: all subjects who signed an informed consent form and received any amount of study drug. Per-Protocol Population: all subjects in the ITT Population who had no major protocol violation during the study. Primary efficacy analysis was not performed for individual dose concentrations.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were collected from catheter placement through 12 months post treatment or early withdrawal and followed until resolution, stabilization, data cut-off, or death. For subjects that withdraw from the study, SAEs that occur within 30 days of the date of discontinuation collected.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MDNA55 (Overall)	24 of 47 (51.1%)	46 of 47 (97.9%)	36 of 47
MDNA55 (1.5 mcg/mL)	7 of 18 (38.9%)	18 of 18 (100%)	16 of 18
MDNA55 (3.0 mcg/mL)	4 of 9 (44.4%)	9 of 9 (100%)	8 of 9
MDNA55 (6.0 mcg/mL)	3 of 6 (50%)	6 of 6 (100%)	3 of 6
MDNA55 (9.0 mcg/mL)	9 of 13 (69.2%)	13 of 13 (100%)	8 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36640127Sampson JH, Singh Achrol A, Aghi MK, Bankiewicz K, Bexon M, Brem S, Brenner A, Chandhasin C, Chowdhary S, Coello M, Ellingson BM, Floyd JR, Han S, Kesari S, Mardor Y, Merchant F, Merchant N, Randazzo D, Vogelbaum M, Vrionis F, Wembacher-Schroeder E, Zabek M, Butowski N. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial. Neuro Oncol. 2023 Jun 2;25(6):1085-1097. doi: 10.1093/neuonc/noac285.
Derived from this study: PubMed 33863808Ellingson BM, Sampson J, Achrol AS, Aghi MK, Bankiewicz K, Wang C, Bexon M, Brem S, Brenner A, Chowdhary S, Floyd JR, Han S, Kesari S, Randazzo D, Vogelbaum MA, Vrionis F, Zabek M, Butowski N, Coello M, Merchant N, Merchant F. Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma. Clin Cancer Res. 2021 Jul 15;27(14):3916-3925. doi: 10.1158/1078-0432.CCR-21-0446. Epub 2021 Apr 16.
Sponsor websiteLink provided by the sponsor.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MDNA55 in people with Glioblastoma and Grade IV Astrocytoma, run by Medicenna Therapeutics, Inc. at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: From start of treatment until date of death from any cause. Subjects who were not known to have died at the time of the analysis were to be censored at the date of last contact.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02858895, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2022.