Clinical trial NCT00089245: Radiolabeled MAB Therapy in 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Memorial Sloan Kettering Cancer Center
First posted: 2004-08-05
Enrollment: 177
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the feasibility and toxicity of administering intrathecal immunotherapy for patients with central nervous system/leptomeningeal (CNS/LM) malignancies.

Detailed description: This is a phase I study, where the purpose 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.

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.

Primary outcomes:
measure: Number of patients that have treatment related toxicities
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Kim Kramer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.