MV-NIS in Treating Children and Young Adults with Recurrent Medulloblastoma or Atypical Teratoid Rhabdoid Tumors
- For stratum A, patients must have local recurrent disease (defined as no evidence of leptomeningeal disease based on negative spine magnetic resonance imaging [MRI] and negative cytology as well as no more than one focal lesion 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 multimodality therapy of surgery, radiation and chemotherapy
- For stratum B and stratum C, 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 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
- 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 * 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 * 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 ** 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 ** 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 * 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 * Bone marrow transplant: Patient must be: ** >= 6 months since allogeneic bone marrow transplant prior to registration ** >= 3 months since autologous bone marrow/stem cell prior to registration
- Patients must have: * Had their last fraction of local irradiation to primary tumor >= 2 weeks prior to registration for local palliative radiation therapy (XRT) (small port) * Had their last fraction of craniospinal irradiation or total body irradiation >= 12 weeks prior to registration
- Karnofsky >= 50 for patients >= 16 years of age, and Lansky >= 50 for patients < 16 years of age; 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 lumbar puncture (LP) as determined by the investigator
- CD4 counts (>= 200/uL)
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to study registration)
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to study registration)
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to study registration): * Age 1 – 2 years - maximum serum creatinine (mg/dL) 0.6 (male and female) * Age 2 to < 6 years - maximum serum creatinine (mg/dL) 0.8 (male and female) * Age 6 to < 10 years - maximum serum creatinine (mg/dL) 1 (male and female) * Age 10 to < 13 years - maximum serum creatinine (mg/dL) 1.2 (male and female) * Age 13 to < 16 years - maximum serum creatinine (mg/dL) 1.5 male and 1.4 female * Age >=16 years - maximum serum creatinine (mg/dL) 1.7 male and 1.4 female
- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to study registration)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (within 7 days prior to study registration)
- Serum albumin >= 2 g/dL (within 7 days prior to study registration)
- Females of child-bearing potential and males 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 female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks prior to entering the study for local palliative XRT (small port) and within 12 weeks prior for patients that received craniospinal XRT
- Patients who have not recovered from acute adverse events due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to measles virus vaccination
- 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
- Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test (within 7 days prior to study registration)
- Patients with known human immunodeficiency virus (HIV)-positivity
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- Exposure to household contact with known immunodeficiency
- History of chronic hepatitis B or C infection
- History of organ transplantation
- Patients with evidence of extraneural disease
- Patients on chronic steroid use or other immunosuppressive agents; note: patients that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids may be eligible, but the study chair must be consulted
- Inability to undergo magnetic resonance (MR) imaging to assess disease status
Salt Lake City
I. To determine the safety and to recommend a phase 2 dose (RP2D) of oncolytic measles virus encoding thyroidal sodium iodide symporter (modified measles virus [MV-NIS]) after a single injection if administered into the tumor bed of patients with locally recurrent medulloblastoma or atypical teratoid rhabdoid tumor (ATRT). (Stratum A)
II. To determine the safety and to recommend a starting dose for stratum C of modified measles virus (MV-NIS) after a single injection if administered into the subarachnoid space of patients with disseminated recurrent medulloblastoma or ATRT. (Stratum B)
III. To determine the safety of two administrations of modified measles virus (MV-NIS) into the subarachnoid space of patients with disseminated recurrent medulloblastoma. (Stratum C)
IV. To determine the progression free survival probability at 4 months (PFS4) in children with disseminated recurrent medulloblastoma. (Stratum C)
I. To preliminarily define the anti-tumor activity of MV-NIS with recurrent medulloblastoma or ATRT within the confines of a phase 1 study by analyzing the objective response rate (ORR), the median progression free survival (PFS), and overall survival (OS).
II. To determine the distribution of MV-NIS after local injection or after administration into the subarachnoid space with single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging.
III. To assess the kinetics of MV-NIS distribution, spread and elimination in nasal swabs, urine, cerebrospinal fluid (CSF), and blood by using quantitative reverse transcription (RT)-polymerase chain reaction (PCR) methods.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 strata.
STRATUM A: Patients with locally recurrent medulloblastoma or ATRT receive oncolytic measles virus encoding thyroidal sodium iodide symporter injected into the tumor bed.
STRATUM B: Patients with recurrent disseminated medulloblastoma or ATRT receive oncolytic measles virus encoding thyroidal sodium iodide symporter via lumbar puncture if a lumbar puncture is performed per standard of care.
STRATUM C: Patients with recurrent disseminated medulloblastoma receive oncolytic measles virus encoding thyroidal sodium iodide symporter via lumbar puncture on days 0 and 7.
After completion of study treatment, patients are followed up every month for 12 months, then every 3 months for up to 24 months.
Trial Phase Phase I
Trial Type Treatment
UCSF Medical Center-Mount Zion
- Primary ID 150812
- Secondary IDs NCI-2017-01831, 16-20133, PNOC 005
- Clinicaltrials.gov ID NCT02962167