Radiolabeled MAB Therapy in Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

NCT00089245 | Terminated Phase 1

• 2 other identifiers: 03-133MSKCC-03133
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of patients that have treatment related toxicities

  Assessment of patient with treatment related toxicities

  2 years

Study Arms (1)

Radiolabeled Monoclonal Antibody Therapy

EXPERIMENTAL

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.

Drug: Iodine I 131 MOAB 8H9

Interventions

Iodine I 131 MOAB 8H9 DRUG

Patients will be injected, intrathecally, with 2 mCi 131I-Omburtamab during week 1 of a 5 week cycle.

Radiolabeled Monoclonal Antibody Therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (2)

• 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.

  PMID: 36371226 DERIVED

• 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.

  PMID: 33047248 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neuroblastoma; Sarcoma; Meningeal Carcinomatosis; Brain Neoplasms; Medulloblastoma; Osteosarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Rhabdoid Tumor; Desmoplastic Small Round Cell Tumor; Rhabdomyosarcoma

Interventions

omburtamab I-131

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue; Meningeal Neoplasms; Brain Diseases; Central Nervous System Diseases; Glioma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Myosarcoma; Neoplasms, Muscle Tissue

Study Officials

• Kim Kramer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: February 5, 2004
• Primary Completion: February 2, 2022
• Study Completion: February 2, 2022
• Last Updated: December 26, 2023

Record last verified: 2023-12

Locations

US (1)