MSC-DNX-2401 in Treating Patients With Recurrent High-Grade Glioma

Phase 1

Recruiting

• Conditions: IDH1 wt Allele; Recurrent Anaplastic Astrocytoma; Recurrent Glioblastoma; Recurrent Gliosarcoma; Recurrent Malignant Glioma

• Registration Number: NCT03896568
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-3-28
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Inclusion Criteria:<br><br>Subjects must meet the following inclusion criteria to be eligible and enroll:<br><br> 1. Subjects must be willing and able to provide informed consent, undergo and comply<br> with all study assessments, and adhere to the protocol schedule.<br><br> 2. Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with<br> recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if<br> there is a significant enhancing mass on MRI (=1.0 cm in diameter with upper limit<br> of 5 cm maximal diameter) because their prognosis/behavior is similar to GBM.<br> Subjects with an initial diagnosis of an IDH-mutant grade 2 or 3 astrocytoma are<br> also eligible at recurrence if a biopsy at recurrence is determined to be IDH-mutant<br> grade 4 astrocytoma, and there is a significant enhancing mass on MRI (=1.0 cm in<br> diameter with upper limit of 5 cm maximal diameter). A pathology report constitutes<br> adequate documentation of histology for study inclusion.<br><br> 3. Patients must show unequivocal evidence for tumor recurrence or progression by MRI<br> scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A<br> baseline MRI must be performed within 24 days prior to registration. Biopsy is<br> encouraged at the time of recurrence if it is unclear that there is recurrent tumor.<br> However, biopsy is not required if the practicing physician thinks that there is<br> adequate radiographic and clinical evidence for recurrence.<br><br> 4. Male or female patients = 18 years of age.<br><br> 5. Patients must be able to undergo endovascular treatment based on Doppler studies<br> showing ICA that is less than 50% occluded.<br><br> 6. For patients undergoing resection for biological endpoints, tumors must be<br> surgically resectable at the time of baseline evaluation and craniotomy for tumor<br> resection is indicated as part of their standard medical care.<br><br> 7. Tumors must be =1.0 cm in diameter with upper limit of 5 cm maximal diameter.<br><br> 8. Patients must have a Karnofsky performance score = 70.<br><br> 9. Patients must have a life expectancy of at least 16 weeks.<br><br> 10. Patients must have adequate bone marrow function (absolute granulocyte count > 1,500<br> and platelet count of > 75,000), adequate liver function (SGPT and SGOT and<br> bilirubin < 2 times institutional normal ranges), and adequate renal function<br> (creatinine < 2.0 times institutional normal) prior to starting therapy.<br><br> 11. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin<br> time (PTT) = 1.5x ULN.<br><br> 12. Subjects who have received the following chemotherapies must have completed them<br> within the following time periods prior to Baseline/Day 0 of hMSC-DNX2401 delivery<br> with recovery from any drug-related toxic effects to Grade 1, or less, severity:<br><br> - Four weeks from cytotoxic agents (3 weeks from procarbazine or Temozolomide, 2<br> weeks from vincristine)<br><br> - 6 weeks from nitrosoureas (CCNU, BCNU)<br><br> - Four weeks from any targeted investigational agent<br><br> - One week from non-cytotoxic agents<br><br> 13. This study was designed to include women and minorities, but was not designed to<br> measure differences of intervention effects. Males and females will be recruited<br> with no preference to gender.<br><br> 14. No exclusion to this study will be based on race. Minorities will actively be<br> recruited to participate. The malignant glioma patient population treated at MDACC<br> over the past year is as follows:<br><br> - American Indian or Alaskan Native - 0<br><br> - Asian or Pacific Islander - <2%<br><br> - Black, not of Hispanic Origin - 3%<br><br> - Hispanic - 6%<br><br> - White, not of Hispanic Origin - 88%<br><br> - Other or Unknown - 2%<br><br> - Total - 100%<br><br> 15. Patients must be 8 weeks from radiotherapy to minimize the potential for MRI changes<br> related to radiation necrosis that might be misdiagnosed as progression of disease,<br> or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is<br> outside the primary radiation field (beyond 80% isodose line). However, if a biopsy<br> is undertaken prior to these times and this biopsy documents histological evidence<br> for recurrent disease, then patients will be eligible regardless of the time after<br> radiation.<br><br> 16. Patients must be willing to forego other cytotoxic and non-cytotoxic drug or<br> radiation therapy against the tumor while enrolled in the study.<br><br> 17. Women of childbearing potential must have a negative urine or serum pregnancy test<br> at screening.<br><br> 18. Subjects and their partners must be willing to use effective birth control during<br> the study and for up to 6 months following administration of hMSC-DNX2401. Birth<br> control that is acceptable to use in this study:<br><br> - Using twice the normal protection of birth control (i.e., double-barrier) by<br> using a condom AND spermicidal jelly or foam, or a diaphragm AND spermicidal<br> jelly or foam. A spermicidal jelly or foam must be used in addition to a<br> barrier method (e.g., condom or diaphragm)<br><br> - Birth control pills (The Pill)<br><br> - Depot or injectable birth control<br><br> - IUD (Intrauterine Device)<br><br> - Birth Control Patch (e.g., Othro Evra®)<br><br> - NuvaRing®<br><br> - Surgical sterilization (i.e., tubal ligation or hysterectomy for women or<br> vasectomy for men)<br><br>Exclusion Criteria:<br><br> 1. Histology other than GBM, gliosarcoma, IDH wild-type astrocytoma grade III or<br> IDH-mutant astrocytoma grade 4.<br><br> 2. Tumor foci detected below the tentorium or beyond the cranial vault.<br><br> 3. Tumor within the posterior fossa.<br><br> 4. Tumor with leptomeningeal spread.<br><br> 5. Difficulty in obtaining vascular access for percutaneous procedure.<br><br> 6. Ipsilateral carotid stenosis (>50%, by Doppler studies).<br><br> 7. Thrombophilias or primary hematological diseases.<br><br> 8. Transfusions or medications (G-CSF) to treat pancytopenia or other hematological<br> conditions < 28 days prior to Baseline/Day 0/hMSC-DNX2401 administration.<br><br> 9. Biologic/immunotherapy within 2 weeks of baseline.<br><br> 10. Clinical or laboratory evidence of inflammatory and/or autoimmune disorders.<br><br> 11. Any contraindication for undergoing MRI such as: individuals with pacemakers,<br> epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel,<br> metal prosthesis, implants with potential magnetic properties, metallic bodies in<br> the eyes, etc. In addition, subjects must present with tumor that is evaluable by<br> MRI.<br><br> 12. Pregnant or nursing females.<br><br> 13. Evidence of active uncontrolled infection or unstable or severe intercurrent medical<br> conditions. All subjects must be afebrile (i.e., <38.0° Celsius [C]).<br><br> 14. Any medical condition that precludes surgery or endovascular treatment<br><br> 15. Alcoholism (dependency), alcohol or substance abuse within twelve (12) months prior<br> to screening that has caused health consequences.<br><br> 16. Immunocompromised subjects or those with autoimmune conditions, active hepatitis<br> (Liver function tests > 2x normal) or human immunodeficiency virus (HIV)<br> seropositivity.<br><br> 17. Evidence of bleeding diathesis or use of anticoagulant medication or any medication<br> t

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum-tolerated dose (MTD);Incidence of adverse events (AEs)

Secondary Outcome Measures

Name	Time	Method
Tumor response;Time to progression;Virus replication in tumor;Virus shedding;Immunogenicity based on adenoviral (AdV) antibodies