Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT (PNOC005)

1. For stratum A, patients must have local recurrent disease (defined as negative spine MRI and negative cytology within 21 days prior to study registration) and undergo resection of local recurrence as part of their standard of care. Children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy.
2. For stratum B, patients must have disseminated recurrent disease (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate cerebrospinal fluid (CSF) flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines. Children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy.
3. Prior Therapy:
   1. The patient must have failed at least one prior therapy - surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy - prior to study registration. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
   2. Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks prior if nitrosourea.
   3. Biologic agent: Patient must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
      1. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
      2. For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
   4. Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such patients should be discussed with the study chair prior to registration. For bevacizumab, patients must have received last dose ≥ 32 days prior to study registration
   5. Bone Marrow Transplant: Patient must be:
      1. ≥ 6 months since allogeneic bone marrow transplant prior to registration
      2. ≥ 3 months since autologous bone marrow/stem cell prior to registration
   6. Radiation: Patients must have:
      1. Had their last fraction of local irradiation to primary tumor ≥12 weeks prior to registration
      2. Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12 weeks prior to registration 
4. Age ≥ 12 months to less than or equal to 39 years of age
5. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age (See Appendix A). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Patients with pre-existing neurological deficits need to be stable prior to surgery or LP as determined by the investigator.
6. Anti-measles virus immunity as demonstrated by IgG anti-measles antibody per institutional guidelines (within 21 days prior to study registration).
7. Organ Function Requirements (within 7 days prior to study registration)
   1. Adequate Bone Marrow Function Defined as:
      1. Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and
      2. Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
   2. Adequate Renal Function Defined as:
      1. Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than or equal to 70mL/min/1.73 m2 or
      2. A serum creatinine based on age/gender as follows:   
         1. Age 1 to 2 years: 0.6 (male), 0.6 (female)
         2. Age 2 to <6 years: 0.8 (male), 0.8 (female)
         3. Age 6 to <10 years: 1.0 (male), 1.0 (female)
         4. Age 10 to <13 years: 1.2 (male), 1.2 (female)
         5. Age 13 to <16 years: 1.5 (male), 1.4 (female)
         6. Age ≥ 16 years: 1.7 (male), 1.4 (female)
   3. Adequate Liver Function Defined as:
      1. Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age and
      2. SGPT (ALT) less than or equal to 110 U/L. and
      3. Serum albumin less than or equal to 2 g/dL.
8. The effects of MV-NIS on the developing human fetus are unknown. For this reason, 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, for the duration of study participation and 4 months after completion of MV-NIS administration. 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.
9. Ability to understand and the willingness to sign a written informed consent document.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

1. Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
2. Patients who are receiving any other investigational agents
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to measles virus vaccination
4. 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 
5. Female patients of childbearing potential must not be pregnant or breast-feeding.
6. Female patients of childbearing potential must have a negative serum or urine pregnancy test (within 7 days prior to study registration)
7. HIV-positive patients
8. Patients with very low CD4 counts (<200/µL or 14% of total lymphocyte count)
9. Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
10. Exposure to household contact with known immunodeficiency
11. Allergy to measles vaccine or history of severe reaction to prior measles vaccination
12. History of chronic hepatitis B or C infection
13. History of organ transplantation
14. Patients with evidence of extraneural disease
15. Patients on chronic steroid use or other immunosuppressive agents

For the most up-to-date list of criteria, please visit clinicaltrials.gov.