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Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

Primary Purpose

Brain and Central Nervous System Tumors, Neuroblastoma, Sarcoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Iodine I 131 MOAB 8H9
Iodine I 131 MOAB 8H9
Sponsored by
Y-mAbs Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring leptomeningeal metastases, recurrent neuroblastoma, disseminated neuroblastoma, recurrent adult brain tumor, recurrent childhood medulloblastoma, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent osteosarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, adult medulloblastoma, previously treated childhood rhabdomyosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, metastatic osteosarcoma, childhood desmoplastic small round cell tumor, metastatic childhood soft tissue sarcoma, adult rhabdomyosarcoma, recurrent adult soft tissue sarcoma, stage IV adult soft tissue sarcoma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Subject Inclusion Criteria: Patients must have a histologically confirmed diagnosis of a malignancy known to be 8H9 reactive. 8H9 expression must be confirmed by immunohistochemical staining of tumor and assessed by the Department of Pathology or by immunofluorescence of bone marrow except for patients confirmed to have neuroblastoma. Patients must have CNS/ leptomeningeal disease which is refractory to conventional therapies or for which no conventional therapy exists OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor). Patients must have no rapidly progressing or deteriorating neurologic examination. Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul. Patients may have active malignancy outside the central nervous system. Both pediatric and adult patients of any age are eligible. Patients or a legal guardian will sign an informed consent form approved by the IRB and obtained by the Principal or a Co- Investigator before patient entry. Minors will provide assent. Patients with stored stem cells will be treated at the escalating dose while patients with no stem cells will be treated at the 50 mCi dose. Neuroblastoma patients can be treated at the 50 mCi dose with or without stored stem cells. Subject Exclusion Criteria: Patients with obstructive or symptomatic communicating hydrocephalus. Patients with an uncontrolled life-threatening infection. Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period. Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol. Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol. Severe major organ toxicity. Specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than grade 2. Patients with stable neurological deficits (because of their brain tumor) are not excluded. Patients with <= 3 hearing loss are not excluded.

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radiolabeled Monoclonal Antibody Therapy

Arm Description

This is a Phase I trial designed to evaluate the Maximally Tolerated Dose (MTD) of intrathecal 131I-8H9. In order to find the MTD, a dose escalation scheme will be employed with patients entering in cohorts of 3 at each dose level from 10 mCi to 60 mCi and a cohort of 6 at each dose level from 70 mCi to 100 mCi.

Outcomes

Primary Outcome Measures

Number of patients that have treatment related toxicities

Secondary Outcome Measures

Full Information

First Posted
August 4, 2004
Last Updated
June 8, 2022
Sponsor
Y-mAbs Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00089245
Brief Title
Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer
Official Title
Phase I Study Of Intrathecal Radioimmunotherapy Using I-8H9 For Central Nervous System/Leptomeningeal Neoplasms
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2004 (undefined)
Primary Completion Date
July 1, 2019 (Actual)
Study Completion Date
July 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Y-mAbs Therapeutics

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to find a safe dose of a new medicine called antibody 8H9. Antibodies are made by the body to fight infections and in some cases, to fight tumors. The antibody 8H9 is made by mice and can attack many kinds of tumors. 8H9 antibody can have a dose of radiation attached to it called 131-I. 131I-8H9 has been given in the vein to patients to find cancer cells. This is the first study using 131I-8H9 in the fluid in the spine to kill cancer cells. 131-I is a beta emitting isotope used extensively for radiation targeted therapies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Neuroblastoma, Sarcoma
Keywords
leptomeningeal metastases, recurrent neuroblastoma, disseminated neuroblastoma, recurrent adult brain tumor, recurrent childhood medulloblastoma, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent osteosarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, adult medulloblastoma, previously treated childhood rhabdomyosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, metastatic osteosarcoma, childhood desmoplastic small round cell tumor, metastatic childhood soft tissue sarcoma, adult rhabdomyosarcoma, recurrent adult soft tissue sarcoma, stage IV adult soft tissue sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Radiolabeled Monoclonal Antibody Therapy
Arm Type
Experimental
Arm Description
This is a Phase I trial designed to evaluate the Maximally Tolerated Dose (MTD) of intrathecal 131I-8H9. In order to find the MTD, a dose escalation scheme will be employed with patients entering in cohorts of 3 at each dose level from 10 mCi to 60 mCi and a cohort of 6 at each dose level from 70 mCi to 100 mCi.
Intervention Type
Drug
Intervention Name(s)
Iodine I 131 MOAB 8H9
Intervention Description
Patients will be injected, intrathecally, with 2 mCi 131I-Omburtamab during week 1 of a 5 week cycle.
Intervention Type
Drug
Intervention Name(s)
Iodine I 131 MOAB 8H9
Intervention Description
The dose used in this study is 50 mCi 131IOmburtamab, (averaging 5 mCi/mg Omburtamab at 50 mCi dose) which will be administered to each patient during week 2 of a 5 week cycle.
Primary Outcome Measure Information:
Title
Number of patients that have treatment related toxicities
Time Frame
2 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Subject Inclusion Criteria: Patients must have a histologically confirmed diagnosis of a malignancy known to be 8H9 reactive. 8H9 expression must be confirmed by immunohistochemical staining of tumor and assessed by the Department of Pathology or by immunofluorescence of bone marrow except for patients confirmed to have neuroblastoma. Patients must have CNS/ leptomeningeal disease which is refractory to conventional therapies or for which no conventional therapy exists OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor). Patients must have no rapidly progressing or deteriorating neurologic examination. Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul. Patients may have active malignancy outside the central nervous system. Both pediatric and adult patients of any age are eligible. Patients or a legal guardian will sign an informed consent form approved by the IRB and obtained by the Principal or a Co- Investigator before patient entry. Minors will provide assent. Patients with stored stem cells will be treated at the escalating dose while patients with no stem cells will be treated at the 50 mCi dose. Neuroblastoma patients can be treated at the 50 mCi dose with or without stored stem cells. Subject Exclusion Criteria: Patients with obstructive or symptomatic communicating hydrocephalus. Patients with an uncontrolled life-threatening infection. Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period. Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol. Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol. Severe major organ toxicity. Specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than grade 2. Patients with stable neurological deficits (because of their brain tumor) are not excluded. Patients with <= 3 hearing loss are not excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim Kramer, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
36371226
Citation
Kramer K, Pandit-Taskar N, Kushner BH, Zanzonico P, Humm JL, Tomlinson U, Donzelli M, Wolden SL, Haque S, Dunkel I, Souweidane MM, Greenfield JP, Tickoo S, Lewis JS, Lyashchenko SK, Carrasquillo JA, Chu B, Horan C, Larson SM, Cheung NV, Modak S. Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies. J Hematol Oncol. 2022 Nov 12;15(1):165. doi: 10.1186/s13045-022-01383-4.
Results Reference
derived
PubMed Identifier
33047248
Citation
Yerrabelli RS, He P, Fung EK, Kramer K, Zanzonico PB, Humm JL, Guo H, Pandit-Taskar N, Larson SM, Cheung NV. IntraOmmaya compartmental radioimmunotherapy using 131I-omburtamab-pharmacokinetic modeling to optimize therapeutic index. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1166-1177. doi: 10.1007/s00259-020-05050-z. Epub 2020 Oct 13.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

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Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

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