Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma

• Status: Suspended
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This single-arm phase II study will assess the impact of tetanus pre-conditioning and adjuvant Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) on overall survival of patients newly diagnosed with World Health Organization (WHO) Grade IV glioblastoma who have undergone definitive tumor resection, are cytomegalvirus (CMV) positive and unmethylated, and completed standard temozolomide (TMZ) and radiation treatment. After completion of the standard of care radiotherapy with concurrent TMZ, patients will receive 1 cycle of dose-intensified TMZ followed by pp65-loaded dendritic cell (DC) vaccination beginning on day 23.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gary Archer Ph.D.
• Treatments: Molgramostim; Sargramostim; Temozolomide; Vaccines

Criteria

Inclusion Criteria:

• Age ≥ 18 years

• Newly diagnosed World Health Organization (WHO) Grade IV Glioma with definitive resection prior to the consent, with a residual radiographic contrast-enhancing disease on the postoperative computed tomography (CT) or Magnetic Resonance Imaging (MRI) of <1 cm in maximal diameter in any plane.

• Able to receive standard of care radiation and chemotherapy for approximately 6 weeks duration and of more than 54GY-MRI post-RT does not show progressive disease at the time of enrollment

• MRI post RT does not show progressive disease outside the radiation field

• Enough tumor tissue available for determination of MGMT gene promoter status (must be unmethylated) or prior pathology report available confirming MGMT gene promoter status

• CMV Seropositive

• KPS of ≥ 70%

• Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/µl, platelets ≥ 100,000 cells/µl prior to starting TMZ cycle 1

• Serum creatinine ≤ 3 times institutional upper limit of normal for age, aspartate aminotransferase (AST) ≤ 3 times institutional upper limit of normal for age, and bilirubin ≤ 1.5 times upper limit of normal prior to starting TMZ cycle 1

• Signed informed consent approved by the Institutional Review Board

• Female patients must not be pregnant or breastfeeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [IUD; only hormonal], sexual abstinence or vasectomized partner) during the trial and for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 48 hours prior to first study procedure (leukapheresis).

• Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, IUDs [only hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of > 6 months following the last administration of trial drugs.

Exclusion Criteria:

• Pregnant or breastfeeding.

• Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.

• Patients with known potentially anaphylactic allergic reactions to gadolinium- diethylenetriamine penta-acetic acid (DTPA).

• Patients who cannot undergo MRI or SPECT due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates).

• Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease.

• Severe, active comorbidity, including any of the following:

1. Unstable angina and/or congestive heart failure requiring hospitalization;

2. Transmural myocardial infarction within the last 6 months;

3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation;

4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy;

5. Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;

6. Known Human Immunodeficiency Virus (HIV) and Hepatitis C positive status;

7. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy;

8. Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity.

• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids

• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. (Treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in the prevention of prior cancer disease recurrence, are not considered current active treatment.)

• Patients are not permitted to have had any other conventional therapeutic intervention other than steroids prior to enrollment outside of the standard of care chemotherapy and radiation therapy. Patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded

• Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study.

• Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus).