Peptide Targets for Glioblastoma Against Novel Cytomegalovirus Antigens

Summary

Participation Requirements

Description

Patients may be enrolled following radiation therapy and prior to initiation of post-radiation therapy cycles of adjuvant TMZ provided they meet all eligibility criteria. After signing main consent, patients will undergo immune monitoring blood work and Tetanus-diphtheria booster vaccination with 0....

Patients may be enrolled following radiation therapy and prior to initiation of post-radiation therapy cycles of adjuvant TMZ provided they meet all eligibility criteria. After signing main consent, patients will undergo immune monitoring blood work and Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, adsorbed). After meeting all eligibility criteria, patients will be randomized to one of two arms: Arm 1 will receive standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28-day cycle) with vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle Arm 2 will receive dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28-day cycle) with vaccination on day 23 (-1 day, +2 days) of each TMZ cycle. Each arm will have approximately 13 patients. For both arms, the patients must be screened at Duke within 3 +/- 1 weeks after completion of standard of care radiation. For both arms, the initial cycle of adjuvant TMZ will begin as soon as possible following randomization. For Arm 1, the adjuvant TMZ cycle(s) will be given as described above. If a patient has an MGMT unmethylated tumor, they will discontinue TMZ after the 1st cycle. All patients will receive a tetanus pre-conditioning injection in the right groin on day 22 (+1 day) of cycle 1 of adjuvant TMZ. On the following day, patients will receive the study vaccine prepared as follows: 500 µg of PEP-CMV Component A mixed with Montanide ISA-51 intradermally administered with half in the right groin and half in the left groin. Vaccines #2 and #3 will be given at 2 week intervals (+ 3 days), which will result in a ~35-day delay before starting TMZ cycle 2. MGMT unmethylated patients will not receive subsequent cycles of TMZ, but will continue to receive vaccines approximately every 4 (+2) weeks. An unacceptable toxicity will be defined as any ? Grade 3 toxicity possibly, probably, or definitely related to the PEP-CMV vaccine with some exceptions. The prevalence of unacceptable toxicities occurring during the vaccinations administered concurrently with temozolomide will be continuously monitored. If more than 25% of accrued patients experience unacceptable toxicities, then accrual will be suspended and reported toxicity will be carefully reviewed to determine if modifications to the protocol treatment should occur. Peptide vaccinations employing Montanide ISA-51 as adjuvants have generally been well tolerated in human patients in numerous phase I-III trials. Patients will be imaged with contrast-enhanced MRI within 2 weeks (+3 days) after vaccine 3 and then approximately every 8 weeks. RANO criteria will be used for assessment of pseudo-progression, and patients demonstrating definitive progression will be removed from study. Blood for immune monitoring will be obtained as well at several time points.

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