Inclusion Criteria:

          -  At the time of surgery, frozen biopsy confirmation of high grade or malignant glioma
             by neuropathologist. Biopsy confirmation of glioma or infiltrative glioma at time of
             surgery will be acceptable, provided that subject has prior pathology confirmation of
             high-grade glioma. If subject had previous diagnosis of low grade glioma, then the
             biopsy must show high grade glioma. To be confirmed at time of surgery, after
             registration in OnCore.

          -  Participants must have prior diagnosis of glioma (astrocytoma, malignant astrocytoma,
             oligodendroglioma, anaplastic oligodendroglioma, mixed oligo-astrocytoma), exclusive
             of ependymoma, ganglioglioma, pylocytic/pylomyxoid astrocytoma as confirmed by a
             neuropathologist or by a previous local pathology report.

          -  Prior history of external beam radiotherapy ≥ 5,000 cGy delivered to the tumor at
             least 4 weeks prior to registration. Participants over the age of 70 with prior
             history of hypofractionated external beam radiotherapy will also be accommodated, in
             accordance with NCCN guidelines; For participants with diagnosis of oliogodendroglioma
             or anaplastic oligodendroglioma, prior history of external beam radiotherapy < 5,000
             cGy or no history of radiation are both acceptable

          -  Prior history of temozolomide chemotherapy provided concurrent to external beam
             radiotherapy and after as per current standard of care. However, temozolomide would
             not be required to have been provided concomitantly or after radiation if the patient
             had unmethylated MGMT promoter or if the patient initially was diagnosed with a low
             grade glioma. At least 4 weeks must have passed from the last dose of temozolomide and
             first dose of cyclophosphamide and/or rQNestin34.5v.2; 3.1.4.1 For participants with
             diagnosis of oliogodendroglioma or anaplastic oligodendroglioma, chemotherapy may have
             been administered before, during, or after radiation or not at all.

          -  If participant was treated with bevacizumab, at least 4 weeks must elapse before
             treatment with either agent (Cyclophosphamide or rQNestin34.5v.2);

          -  Recurrent lesion must be ≥ 1.0 cm in diameter as determined by MRI;

          -  Normal hematological, renal and liver function as defined below: Leukocytes
             ≥3,000/mcL; Absolute lymphocyte count > 500/ mcL; Absolute neutrophil count
             ≥1,500/mcL; platelets ≥100,000/mcL; PT or PTT <1.5 x institutional upper limit;
             Hemoglobin >10.0 g/dL; Total serum bilirubin within normal institutional limits;
             AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal; Serum creatinine
             within normal institutional limits OR Creatinine clearance ≥60 mL/min/1.73 m2 for
             participants with creatinine levels above institutional normal;

          -  Karnofsky Performance Score ≥70.

          -  Age ≥ 18 years;

          -  Ability to understand and the willingness to sign a written informed consent document;

          -  The effects of rQNestin34.5v.2 and cyclophosphamide on the developing human fetus are
             unknown. For this reason and because cytotoxic & immunomodulating agents as well as
             other therapeutic agents used in this trial are known to be teratogenic, women of
             child-bearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation including 3 months following the study. Should a woman become
             pregnant or suspect she is pregnant while she or her partner is participating in this
             study, she should inform her treating physician immediately. Men treated or enrolled
             on this protocol must also agree to use adequate contraception prior to the study and
             for the duration of study participation including 3 months following the study. Women
             of child-bearing potential must have a negative serum pregnancy test within 48 hours
             of study registration.

          -  Steroid regimen stable or decreasing for at least 7 days prior to inoculation;

          -  Ability to undergo MRI scanning with contrast;

          -  Subjects with any recurrence (first, second, third, etc recurrence) will be able to be
             enrolled.

        Exclusion Criteria:

        Participants who exhibit any of the following conditions prior to initiating study
        treatment will not be eligible for this study:

          -  Participants with significant renal or liver disease

          -  Participants with progressive systemic malignancy.

          -  Known chronic infections with HIV, hepatitis B or C; participants with a history of
             resolved Hepatitis A may be included in the trial.

          -  Participants with active viral, bacterial or fungal infection requiring concurrent
             antiviral or antibiotics.

          -  Subjects with active HSV1 infection on current valacyclovir, acyclovir or ganciclovir
             therapy must be off treatment with any of these agents at least 7 days prior to
             surgery.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to cyclophosphamide (only for arm B).

          -  Active, known, or suspected immunosuppressive disorders, such as acquired or
             congenital immune deficiency syndromes and autoimmune diseases

          -  Unacceptable anesthesia risk

          -  Serious cardiopulmonary medical condition

          -  Pregnant or lactating females

          -  Recurrent glioma where injection in either arm A or B of the biologic agent would
             require access and/or considerable spillage into the ventricular system.

          -  Prior participant in another protocol using an investigational agent or device within
             5 half-lives or 4 weeks of the investigational agent, whichever is shorter.

          -  Known HIV seropositivity.

          -  Concurrent therapy with drugs active against HSV (acyclovir, valaciclovir,
             penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). Participants must be off
             treatment with these agents for at least 7 days prior to surgery.

          -  Active oral or genital herpes lesions.

          -  Participants who have had chemotherapy or radiotherapy within 4 weeks prior to
             entering the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Participants who are receiving any other investigational agents. Previous
             rQNestin34.5v.2 participants may be re-enrolled if they completed at least the day 56
             assessment without DLT.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Participants with tumor ≤ 1 cm proximity to the ventricles will be allowed to enroll.
             However the study agent (rQNestin34.5v.2) may not be injected in any area that is
             within 1 cm of the ventricle regardless of where the tumor is located.