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

Phase 1

Terminated

• Conditions: Sarcoma; Brain and Central Nervous System Tumors; Neuroblastoma
• Interventions: Drug: Iodine I 131 MOAB 8H9

• Registration Number: NCT00089245
• Lead Sponsor: Y-mAbs Therapeutics

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.

Study Timeline

• Study Start: 2004-02-05
• Study First Submitted: 2004-08-04
• Study First Submitted QC: 2004-08-04
• Study First Posted: 2004-08-05
• Primary Completion: 2022-02-02
• Study Completion: 2022-02-02
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-18
• Last Update Posted: 2023-12-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 177

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiolabeled Monoclonal Antibody Therapy	Iodine I 131 MOAB 8H9	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.

Primary Outcome Measures

Name	Time	Method
Number of patients that have treatment related toxicities	2 years	Assessment of patient with treatment related toxicities

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States