新規診断膠芽腫に対する標準治療化学放射線療法に加えたBvax（B細胞ワクチン）の第I相初回ヒト試験 (Bvax)

Inclusion Criteria (for study participation)

1. Histologically confirmed glioblastoma.

   a. Adequate tissue is required for confirmation of diagnosis; a formalin-fixed and paraffin-embedded (FFPE) tissue block must be available for confirmation of diagnosis and possible additional molecular studies (if applicable)

2. Fresh frozen tumor tissue available for preparation of vaccine (minimum of 1.5 grams) as detailed in the investigator's brochure (IB).

3. No prior therapy other than surgery, or first-line therapy with standard chemoradiation.

4. Age ≥ 18 years.

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

6. Adequate organ and bone marrow function NOTE: Transfusions or growth factors to boost counts to an eligible level are not allowed.

7. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

8. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.

9. The effects of Bvax on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, females of child-bearing potential (FOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of informed consent, for the duration of study participation, and for 90 days following last dose of therapy.

   1. Should a female patient become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
   2. Men treated or enrolled on this protocol must also agree to use adequate contraception from the time of informed consent, for the duration of study participation, and 3 months after completion of administration.

   NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

   • Has not undergone a hysterectomy or bilateral oophorectomy
   • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months) FOCBP must have a negative pregnancy test before registration in the study.

10. The ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Have not recovered from adverse events from surgery or the ongoing chemoradiotherapy (i.e., have residual toxicities > Grade 2) with the exception of alopecia.

2. Receiving any other investigational agents.

3. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to Bvax.

   a. The Bvax drug product consists of: i. Active cellular component: Autologous CD19+ (4-1BBL+) B cells pulsed with autologous tumor lysate.

   ii. Cryopreservation medium: CryoStor® CS10 (BioLife Solutions), a current Good Manufacturing Practice (cGMP)-grade, serum-free cryoprotectant containing 10% dimethyl sulfoxide (DMSO).

   iii. Container closure system: OriGen Biomedical CryoStor® EVA freezing bag, made from biocompatible ethylene vinyl acetate (EVA).

4. There are no animal-derived proteins, adjuvants, or foreign biologicals in the final drug product. Therefore, "compounds of similar chemical or biological composition" specifically refers to:

   i. DMSO or DMSO-containing cryoprotectants, as hypersensitivity to DMSO has been reported in other cryopreserved cell therapy products.

   ii. Excipients within CryoStor® CS10, which include pharmaceutical-grade buffer salts and electrolytes.

   iii. EVA (ethylene vinyl acetate) materials used in the cryostorage bag, for individuals with rare known contact allergies to plastics or related compounds.

5. An uncontrolled intercurrent illness, including, but not limited to, the following:

   1. Ongoing or active infection requiring systemic treatment
   2. Symptomatic congestive heart failure
   3. Unstable angina pectoris
   4. Cardiac arrhythmia
   5. Psychiatric illness/social situations that would limit compliance with study requirements
   6. Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

6. Psychiatric illness/social situations that would limit compliance with study requirements.

7. Female patients who are pregnant or nursing. Pregnant or nursing women are excluded from this study because of the unknown risks of the study products.