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

NCT02962167 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: PNOC 005150812NCI-2017-01831
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 8

Brief Summary

This is a three 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).

Conditions

Medulloblastoma, Childhood, Recurrent; Atypical Teratoid/Rhabdoid Tumor; Medulloblastoma Recurrent

Keywords

measles virus; recurrent medulloblastoma; recurrent ATRT

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Adverse Events as Assessed by CTCAE v5.

  The safety of the modified measles virus will be assessed by monitoring for adverse events. Subjects will be monitored for adverse events via scheduled laboratory assessments, vital sign measurements, and physical examinations. The severity of any toxicity will be graded according to the NCI CTCAE v5.0. We will aggregate this information into the number of subjects with adverse events that are related to study treatment.

  12 months

• Recommended Phase 2 Dose.

  The maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) will be the dose level at which 6 evaluable patients have been treated and at most 1 patient experienced a dose limiting toxicity (DLT) and the next highest dose level is too toxic or we have reached the protocol defined highest dose level.

  12 months

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  24 months

• Progression Free Survival (PFS)

  24 months

Other Outcomes (1)

• The distribution of MV-NIS

  12 months

Study Arms (3)

Locally Recurrent Medulloblastoma/ATRT

EXPERIMENTAL

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. Patients 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. Patients will receive the modified measles virus, MV-NIS, directly into the tumor bed during standard of care resection.

Biological: Modified Measles Virus

Disseminated Recurrent MB/ATRT

EXPERIMENTAL

Patients must have disseminated recurrent medulloblastoma (MB) or ATRT (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. Patients 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. Patients will receive the modified measles virus, MV-NIS, via lumbar puncture (modified measles virus lumbar puncture).

Biological: Modified Measles Virus Lumbar Puncture

Disseminated Recurrent Medulloblastoma

EXPERIMENTAL

Patients must have disseminated recurrent medulloblastoma (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. Patients 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. Patients will receive the modified measles virus, MV-NIS, via lumbar puncture (modified measles virus lumbar puncture).

Biological: Modified Measles Virus Lumbar Puncture

Interventions

Modified Measles Virus BIOLOGICAL

Administration of MV-NIS either into the tumor bed, if surgery to remove local tumor

Also known as: MV-NIS

Locally Recurrent Medulloblastoma/ATRT

Modified Measles Virus Lumbar Puncture BIOLOGICAL

Administration of MV-NIS into the cerebrospinal fluid via lumbar puncture

Also known as: MV-NIS LP

Disseminated Recurrent MB/ATRT; Disseminated Recurrent Medulloblastoma

Eligibility Criteria

• Age: 12 Months - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• For 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 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.
• o Biologic agent: Patient must have recovered from any acute 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
• Radiation:
• Patients must have:

You may not qualify if:

• 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 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 steroids 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.
• Inability to undergo magnetic resonance (MR) imaging to assess disease status

Sponsors & Collaborators

• Sabine Mueller, MD, PhD: lead
• No More Kids With Cancer: collaborator
• The Matthew Larson Foundation for Pediatric Brain Tumors: collaborator
• Vyriad, Inc.: collaborator
• Mayo Clinic: collaborator

Study Sites (8)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Medulloblastoma; Recurrence; Rhabdoid Tumor

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Complex and Mixed

Study Officials

• Sabine Mueller, MD, PhD, MAS

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Adjunct Professor

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 11, 2016
• Study Start: February 22, 2017
• Primary Completion: May 10, 2023
• Study Completion: May 10, 2023
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)