Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma
Condition: Glioblastoma; Grade IV Astrocytoma; Glioblastoma Multiforme; Grade IV Glioma
MeSH terms: Glioblastoma; Glioma; Astrocytoma
Intervention: MDNA55
Intervention description: MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the pseudomonas exotoxin A (PE).
Intervention MeSH terms: Interleukin-4
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        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