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

Status: Recruiting
Phase:
DFCI Protocol ID: 17-103

This is a two arm Phase I study within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). This study will look to determine the safety and recommended phase 2 dose of the modified measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma or atypical teratoid rhabdoid tumor (ATRT).

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Susan Chi, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  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.

  -  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.

Prior Therapy:

  -  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.

     o 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.

     o 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.

     o 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

  -  Radiation:

Patients must have:

  -  Had their last fraction of local irradiation to primary tumor ≥12 weeks prior to
     registration

  -  Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12
     weeks prior to registration

     • Age ≥ 12 months to less than or equal to 39 years of age

     • 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.

       -  Anti-measles virus immunity as demonstrated by IgG anti-measles antibody per
  institutional guidelines (within 21 days prior to study registration).

       -  Organ Function Requirements (within 7 days prior to study registration)

  -  Adequate Bone Marrow Function Defined as:

     - Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and

     - Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving
     platelet transfusions for at least 7 days prior to enrollment).

  -  Adequate Renal Function Defined as:

       -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater
  than or equal to 70mL/min/1.73 m2 or

       -  A serum creatinine based on age/gender as follows:

Age

Maximum Serum

Creatinine (mg/dL)

Male Female

  1. - 2 years 0.6 0.6

  2. to < 6 years 0.8 0.8

6 to < 10 years 1 1

10 to < 13 years 1.2 1.2

13 to < 16 years 1.5 1.4

  -  16 years 1.7 1.4 The threshold creatinine values in this table were derived from the
     Schwartz formula for estimating GFR utilizing child length and stature data published
     by the CDC.

       -  Adequate Liver Function Defined as:

  - Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper
  limit of normal (ULN) for age and

  - SGPT (ALT) less than or equal to 110 U/L. and

  - Serum albumin less than or equal to 2 g/dL.

  • 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.

  • Ability to understand and the willingness to sign a written informed consent
  document.

  -Exclusion Criteria

  -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

  -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)

  -HIV-positive patients

    -  Patients with very low CD4 counts (<200/µL or 14% of total lymphocyte count)

    -  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

    -  Allergy to measles vaccine or history of severe reaction to prior measles
       vaccination

    -  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

Know Your Options

Not sure which clinical trials might be right for your child? Email our clinical trials team at clinicaltrials@danafarberbostonchildrens.org.
We can help you navigate your options.

Get Clinical Trial Updates

 

Stay informed about Dana-Farber/Boston Children's research efforts, including information on new and current clinical trials. Sign up to receive our email newsletter Advances in Pediatric Hematology/Oncology.

Download Our Clinical Trials

Download a list of our open clinical trials. Check back regularly for updates.