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177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma

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ClinicalTrials.gov Identifier: NCT04167618
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Tracking Information
First Submitted Date  ICMJE November 11, 2019
First Posted Date  ICMJE November 19, 2019
Last Update Posted Date November 24, 2021
Actual Study Start Date  ICMJE September 30, 2021
Estimated Primary Completion Date December 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 1 year ]
    Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1
  • Incidence of AEs and SAEs [ Time Frame: 2 years ]
    In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
    The time for maximum absorbed radiation dose
  • Analysis of lutetium-177 activity in blood [ Time Frame: 2 weeks ]
    Elimination half-life of radioactivity
  • Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
    Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
  • Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
    Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
  • Maximum Plasma Concentration [Cmax] in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF
  • Maximum Plasma Concentration [Cmax] in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum
  • Elimination Half Life in CSF [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in CSF
  • Elimination Half Life in serum [ Time Frame: 7 weeks ]
    Concentration of 177Lu-DTPA-omburtamab in serum
  • Response [ Time Frame: 2 years ]
    Objective Response Rate (ORR) is defined as partial response (PR) or complete response (CR) and as defined by the Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria (as determined from magnetic resonance imaging [MRI] assessments), neurological examination, and cerebrospinal fluid (CSF) cytology
  • Investigator-assessed duration of response (DoR) [ Time Frame: 2 years ]
    DoR is defined as the time from response (CR or PR) to progression
  • Progression Free Survival (PFS) [ Time Frame: 2 years ]
    PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first
  • Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from first treatment until death
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Pharmacokinetic analysis of lutetium-177 in blood [ Time Frame: 2 weeks ]
    The time for maximum absorbed radiation dose
  • Pharmacokinetic analysis of lutetium-177 in blood [ Time Frame: 2 weeks ]
    Elimination half-life of radioactivity
  • Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
    Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
  • Dosimetry analysis of lutetium-177 [ Time Frame: 2 weeks ]
    Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
  • Objective Response Rate (ORR) [ Time Frame: 1 year (Part 1); 2 years (Part 2) ]
    ORR is defined as partial response (PR) or complete response (CR) and as defined by the Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria (as determined from magnetic resonance imaging [MRI] assessments) and cerebrospinal fluid (CSF) cytology
  • Progression Free Survival (PFS) [ Time Frame: 1 year (Part 1); 2 years (Part 2) ]
    PFS is defined as the time from the first treatment to date of progression or death from any cause, whichever comes first
  • Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from first treatment until death from any cause
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 177Lu-DTPA-Omburtamab Radioimmunotherapy for Recurrent or Refractory Medulloblastoma
Official Title  ICMJE A Phase I/II Dose-escalation and Expansion Cohort Trial of Intracerebroventricular Radioimmunotherapy Using 177Lu-DTPA-Omburtamab in Pediatric and Adolescent Patients With Recurrent or Refractory Medulloblastoma
Brief Summary Children and adolescents diagnosed with medullablastoma and with recurrent or refractory to frontline therapy will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.
Detailed Description

Part 1 is a dose-escalation phase with a 3+3 sequential-group design in which patients will receive a dosimetry dose followed by maximum of two 5-week cycles of treatment doses of intracerebroventricular 177Lu-DTPA-omburtamab.

Part 2 is a cohort-expansion phase in which patients will receive a maximum of five 5-week cycles of intracerebroventricular 177Lu-DTPA-omburtamab at the recommended dose determined in Part 1.

End of treatment will take place within 5 weeks after the last cycle and thereafter the patients will be enter the follow-up period. The patients will be followed for up to 2 years after last dose.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Patients will receive up to two cycles in Part 1 and up to five cycles in Part 2 of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Medulloblastoma, Childhood
Intervention  ICMJE Drug: 177Lu-DTPA-omburtamab
Biological, radiolabeled DPTA-omburtamab
Study Arms  ICMJE Experimental: 177Lu-DTPA-omburtamab
Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to two cycles (Part 1) and up to five cycles (Part 2).
Intervention: Drug: 177Lu-DTPA-omburtamab
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 14, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2024
Estimated Primary Completion Date December 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis of medulloblastoma.
  • SHH, Group 3, or Group 4 according to World Health Organisation (WHO) 2016 classification.
  • Recurrent (maximum of 2 recurrences for Part 1 and 1 recurrence for Part 2) or refractory to frontline therapy. Prior frontline or second line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
  • Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously.
  • Performance status score of 50 to 100 on Lansky (less than 16 years) or Karnofsky (16 years or older) scales.
  • Life expectancy of at least 3 months, as judged by the Investigator.
  • Acceptable hematological status and liver and kidney function.

Exclusion Criteria:

  • Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya patency/cerebrospinal fluid (CSF) flow study.
  • Residual disease (nodular or linear) measuring > 15 mm in the smallest diameter.
  • Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts.
  • Grade 4 nervous system disorder. Stable neurological deficits (due to brain tumor or surgery) or hearing loss are allowed.
  • Uncontrolled life-threatening infection.
  • Received radiation therapy less than 3 weeks prior to the screening visit.
  • Received systemic or intrathecal cytotoxic chemotherapy or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the screening visit.
  • Received any prior anti-B7-H3 treatment.
  • Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity.
  • Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com
Listed Location Countries  ICMJE Denmark,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04167618
Other Study ID Numbers  ICMJE 301
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: Undecided
Responsible Party Y-mAbs Therapeutics
Study Sponsor  ICMJE Y-mAbs Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Y-mAbs Therapeutics
Verification Date November 2021

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