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Trial record 1 of 1 for:    MDNA-55
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Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02858895
Recruitment Status : Completed
First Posted : August 8, 2016
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Medicenna Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 28, 2016
First Posted Date  ICMJE August 8, 2016
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE April 11, 2017
Actual Primary Completion Date September 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
Overall Survival (OS) [ Time Frame: 12 months ]
OS, time from treatment until death
Original Primary Outcome Measures  ICMJE
 (submitted: August 3, 2016)
Objective Response Rate (ORR) [ Time Frame: 12 months ]
ORR, determined by independent blinded review
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • Objective Response Rate (ORR) [ Time Frame: 12 months ]
    ORR, determined by independent central review (per RANO-based criteria)
  • Progression Free Survival (PFS) [ Time Frame: 12 months ]
    PFS, time from treatment until disease progression (per RANO-based criteria) or death
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2016)
  • Overall Survival (OS) [ Time Frame: 12 months ]
    OS, time from treatment until death
  • Progression Free Survival (PFS) [ Time Frame: 12 months ]
    PFS, time from treatment until disease progression or death
Current Other Pre-specified Outcome Measures
 (submitted: May 15, 2018)
  • Serious adverse events (SAEs) [ Time Frame: 12 months ]
    Incidence of SAEs
  • Treatment emergent adverse events (AEs) [ Time Frame: 12 months ]
    Incidence of Treatment-Emergent AEs
  • Pharmacokinetics (PK) of MDNA55 [ Time Frame: 14 days ]
    Blood samples will be collected to determine levels of MDNA55
  • Anti-MDNA55 antibody [ Time Frame: 12 months ]
    Blood samples will be collected to determine anti-drug antibody titers
Original Other Pre-specified Outcome Measures
 (submitted: August 3, 2016)
  • Duration of response (DOR) [ Time Frame: 12 months ]
    DOR, time from treatment until disease progression or death among those subjects achieving a complete response (CR) or partial response (PR) to treatment
  • Duration of clinical benefit (DOCB) [ Time Frame: 12 months ]
    DOCB, time from treatment until disease progression or death among those subjects achieving a complete response (CR), partial response (PR), or stable disease (SD)
  • Serious adverse events (SAEs) [ Time Frame: 12 months ]
    Incidence of SAEs
  • Treatment emergent adverse events (AEs) [ Time Frame: 12 months ]
    Incidence of Treatment-Emergent AEs
  • Electrocardiogram (ECG) [ Time Frame: 0-2 days ]
    Incidence of clinically significant ECG findings
  • Karnofsky Performance Score (KPS) [ Time Frame: 12 months ]
    Changes since baseline
  • Detection of MDNA55 in serum [ Time Frame: 14 days ]
    Serum samples will be collected to determine levels of MDNA55 in serum
  • Anti-MDNA55 antibody [ Time Frame: 12 months ]
    Serum samples will be collected to determine anti-drug antibody titers
  • Neutralizing antibody titer [ Time Frame: 12 months ]
    If presence of anti-MDNA55 antibody is found in any sample analyzed, further immunogenicity assessments will be carried out for determination of antibody neutralization potential
 
Descriptive Information
Brief Title  ICMJE Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma
Official Title  ICMJE An Open-Label Non-Randomized, Multi-Center Phase-2 Study of Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma
Brief 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 previous standard or investigational lines of therapy.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Grade IV Astrocytoma
  • Glioblastoma Multiforme
  • Grade IV Glioma
Intervention  ICMJE Drug: MDNA55
MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).
Other Names:
  • IL4-PE
  • Interleukin-4 Pseudomonas Exotoxin
  • Interleukin-4 Pseudomonas Toxin
  • IL4 Pseudomonas Exotoxin
  • NBI-3001
  • cpIL4-PE
Study Arms  ICMJE Experimental: MDNA55

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

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

Intervention: Drug: MDNA55
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 1, 2019)
46
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2016)
43
Actual Study Completion Date  ICMJE October 31, 2019
Actual Primary Completion Date September 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Poland
 
Administrative Information
NCT Number  ICMJE NCT02858895
Other Study ID Numbers  ICMJE MDNA55-05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Medicenna Therapeutics, Inc.
Study Sponsor  ICMJE Medicenna Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Medicenna Therapeutics, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP