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

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ClinicalTrials.gov Identifier: NCT02962167
Recruitment Status : Recruiting
First Posted : November 11, 2016
Last Update Posted : February 22, 2019
Sponsor:
Collaborators:
No More Kids With Cancer
The Matthew Larson Foundation for Pediatric Brain Tumors
Vyriad, Inc.
Mayo Clinic
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE November 2, 2016
First Posted Date  ICMJE November 11, 2016
Last Update Posted Date February 22, 2019
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Number of Participants with Adverse Events as Assessed by CTCAE v4. [ Time Frame: 12 months ]
    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 v4.0. We will aggregate this information into the number of subjects with adverse events that are related to study treatment.
  • Recommended Phase 2 Dose. [ Time Frame: 12 months ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2016)
  • Number of Participants with Adverse Events as Assessed by CTCAE v4. [ Time Frame: 12 months ]
    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 v4.0. We will aggregate this information into the number of subjects with adverse events that are related to study treatment.
  • Recommended Phase 2 Dose. [ Time Frame: 12 months ]
    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 DLT and the next highest dose level is too toxic or we have reached the protocol defined highest dose level.
Change History Complete list of historical versions of study NCT02962167 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2016)
  • Objective Response Rate (ORR) [ Time Frame: 24 months ]
    Any eligible patient that receives MV-NIS will be considered evaluable for clinical efficacy. The objective response criteria is that partial response (PR) and complete response (CR) must be confirmed at least 8 weeks after the initial PR or CR criteria is met.
  • Progression Free Survival (PFS) [ Time Frame: 24 months ]
    For patients who are still progression free at the time of analysis, PFS will be censored at the last contact date. PFS will be estimated using the Kaplan-Meier method.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 17, 2018)
The distribution of MV-NIS [ Time Frame: 12 months ]
Subjects who consent to this optional study will receive an injection of technetium-99m (TC-99m) (pertechnetate) and then undergo SPECT imaging to determine MV-NIS distribution after local injection or after administration into the subarachnoid space.
Original Other Pre-specified Outcome Measures
 (submitted: November 8, 2016)
The distribution of MV-NIS [ Time Frame: 12 months ]
Subjects who consent to this optional study will receive an injection of TC-99m (pertechnetate) and then undergo SPECT imaging to determine MV-NIS distribution after local injection or after administration into the subarachnoid space.
 
Descriptive Information
Brief Title  ICMJE Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT
Official Title  ICMJE A Phase 1 Study of Modified Measles Virus (MV-NIS) for the Treatment of Children and Young Adults With Recurrent Medulloblastoma or Recurrent Atypical Teratoid Rhabdoid Tumors (ATRT)
Brief Summary

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).

Detailed Description

This is an open label, multi-center, Phase I study to assess the safety of administering MV-NIS directly into the tumor bed (for locally recurrent medulloblastoma or ATRT patients) or into the subarachnoid space (for disseminated recurrent medulloblastoma or ATRT patients).

For locally recurrent patients, MV-NIS will be directly administered into the tumor bed following a standard of care surgical resection. For patients with disseminated recurrence, MV-NIS will be injected via lumbar puncture (LP). This is a one-time administration for either locally or disseminated recurrence.

Patients will be closely monitored for 30 days after injection, and then followed for evaluation of 6 month progressive free survival and overall response rate.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Medulloblastoma, Childhood, Recurrent
  • Atypical Teratoid/Rhabdoid Tumor
  • Medulloblastoma Recurrent
Intervention  ICMJE
  • Biological: Modified Measles Virus
    Administration of MV-NIS either into the tumor bed, if surgery to remove local tumor
    Other Name: MV-NIS
  • Biological: Modified Measles Virus Lumbar Puncture
    Administration of MV-NIS into the cerebrospinal fluid via lumbar puncture
    Other Name: MV-NIS LP
Study Arms  ICMJE
  • Experimental: Locally Recurrent Medulloblastoma/ATRT
    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.
    Intervention: Biological: Modified Measles Virus
  • Experimental: Disseminated Recurrent MB/ATRT
    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).
    Intervention: Biological: Modified Measles Virus Lumbar Puncture
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 8, 2016)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 immunoglobulin G (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 70 milliliters (mL)/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 Centers for Disease Control and Prevention (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

      - serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (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 cluster of differentiation 4 (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 39 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sabine Mueller, MD, PhD, MAS (415) 476-3831 sabine.mueller@ucsf.edu
Contact: Lajhem Cambridge, MS (415) 502-1600 lajhem.cambridge@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02962167
Other Study ID Numbers  ICMJE PNOC 005
150812 ( Other Identifier: University of California, San Francisco )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • No More Kids With Cancer
  • The Matthew Larson Foundation for Pediatric Brain Tumors
  • Vyriad, Inc.
  • Mayo Clinic
Investigators  ICMJE
Study Chair: Sabine Mueller, MD, PhD, MAS University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP