Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens

• Status: Active, not recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Newly diagnosed glioblastoma (GBM) patients with complete or partial surgical resection who are CMV seropositive patients will be eligible to enroll on this trial. Patients will be enrolled following standard of care chemoradiation and prior to initiation of post-radiation cycles of temozolomide (TMZ) provided they meet all eligibility criteria. Eligible patients will receive a tetanus-diphtheria (Td) vaccination. Patients will then be randomized to one of two arms of the study: Arm 1 will received standard TMZ and Arm 2 will receive dose-intensified TMZ. All patients will receive a pre-conditioning injection of tetanus on day 22 of the first post-radiation cycle of TMZ. The following day, patients will receive the first of 3 intradermal (i.d.) injections of the study drug cytomegalovirus peptide (PEP-CMV), which contains what is referred to as Component A. Vaccines #2 and #3 will be given at 2 week intervals. Patients who are MGMT (O[6]-methylguanine-DNA methyltransferase) unmethylated will receive one adjuvant cycle of the TMZ regimen according to their assigned randomized arm. Patients who are MGMT methylated or whose methylation status is inconclusive will continue with up to 12 cycles of TMZ. After the completion of a patient's last TMZ cycle, vaccines will continue every 4-6 weeks for a maximum number of 20 vaccines (unless tumor progression occurs).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gary Archer Ph.D.
• Collaborators: Annias Immunotherapeutics, Inc.; National Cancer Institute (NCI); National Institutes of Health (NIH)
• Treatments: Dacarbazine; Temozolomide

Criteria

Inclusion Criteria:

1. Age ≥ 18 years.

2. Histopathologically proven newly-diagnosed primary glioblastoma with complete or partial surgical resection. Biopsy not acceptable.

3. Patients must be CMV seropositive.

4. The tumor must be supratentorial.

5. Karnofsky performance status of ≥ 70.

6. Stable or decreasing steroid dose (≤ 4 mg/day) at time of post-XRT adjuvant TMZ initiation. If patients are decreasing steroid use, once they are at 2 mg/day, they may be supplemented with physiologic replacement hydrocortisone therapy (20-30 mg/day in divided doses), at the discretion of the treating oncologist.

7. Hematology: ANC ≥ 1500 cells/µL, Platelet count ≥ 100,000 cells/µL, Hemoglobin ≥ 9.0 g/dl

8. Chemistry: ALT/AST ≤ 3.0 times the upper limit of normal (ULN), Total bilirubin ≤ 1.5 mg x ULN (Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)

Exclusion Criteria:

1. Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry.

2. Prior conventional antitumor therapy, other than steroids, RT or TMZ therapy given for glioblastoma.

3. Pregnant or need to breast feed during the study period.

4. Not adhering to pregnancy prevention recommendations.

5. Active infection requiring intravenous antibiotics or an unexplained febrile (> 101.5 F) illness.

6. Immunosuppressive disease or human immunodeficiency virus infection.

7. Patients with unstable or severe intercurrent medical conditions such as severe heart or lung disease.

8. Allergic or unable to tolerate TMZ for any reason. Any patient that successfully completed at least 5 weeks of Temodar during standard of care XRT/TMZ and whose blood counts meet the eligibility requirements (inclusion #7) within 4 weeks post XRT/TMZ is eligible.

9. Patients with previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies.

10. Prior allogeneic solid organ transplant.

11. Currently receiving or ever received immunosuppressive therapy for an autoimmune disorder or an organ transplant.