The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine in combination with vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, in adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.
This study is designed to assess the safety and efficacy of the PEPIDH1M vaccine in combination with vorasidenib in adult patients recurrent IDH1 mutant lower grade gliomas. Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Patients will then receive vorasidenib 40 mg orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day 15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning injection of a single dose of Td toxoid (1 flocculation unit \[Lf\] in a total volume of 0.4 mL saline). This will be administered twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total of 14 cycles of vorasidenib. Notably, a safety lead-in will be performed before commencing on the full study to assess the safety of the combination and evaluation for any dose-limiting toxicity (DLT). The most common side effects of peptide vaccines are redness or swelling at the injection site, local changes to the texture of skin (hardening) at the injection site, itching, allergic reactions, and a potentially serious side effect called cytokine release syndrome. The most common side effects of vorasidenib are abnormal liver function tests, QT prolongation, stomach and/or intestinal ulcers, neurologic disturbances, skin peeling, and isocitrate dehydrogenase (IDH) differentiation syndrome. All patients who receive any protocol treatment will be included in either primary or secondary efficacy analyses. Statistical analyses for the primary objective of adverse experience will exclude patients who terminate protocol treatment prematurely (i.e., less than 4 vaccinations) without an unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids) intramuscularly into the deltoid muscle. Patients will then receive vorasidenib 40mg orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day 15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning injection of a single dose of Td toxoid. This will be administered twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total of 14 cycles of vorasidenib.
Duke University Medical Center
Durham, North Carolina, United States
RECRUITINGTo assess the safety of the PEPIDH1M vaccine in combination vorasidenib in adult patients with progressive IDH1 mutant World Health Organization (WHO) Grade 2-3 gliomas
The proportion of patients with an unacceptable toxicity
Time frame: 3.5 years
Describe the efficacy, as measured by progression-free survival (PFS), of the combination of PEPIDH1M vaccine and vorasidenib in adult patients with recurrent IDH1 lower grade glioma
The time between initiation of cycle 1 vorasidenib and first documentation of disease progression or death
Time frame: 10 years
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