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

Sponsor

Y-mAbs Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT00089245

Collaborator

(none)

120

Enrollment

Location

Arm

252

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Neuroblastoma Sarcoma	Drug: Iodine I 131 MOAB 8H9 Drug: Iodine I 131 MOAB 8H9	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study Of Intrathecal Radioimmunotherapy Using I-8H9 For Central Nervous System/Leptomeningeal Neoplasms

Study Start Date :

Jul 1, 2004

Actual Primary Completion Date :

Jul 1, 2019

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiolabeled Monoclonal Antibody Therapy 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 Patients will be injected, intrathecally, with 2 mCi 131I-Omburtamab during week 1 of a 5 week cycle. Drug: Iodine I 131 MOAB 8H9 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.

Arm

Intervention/Treatment

Experimental: Radiolabeled Monoclonal Antibody Therapy

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

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

Drug: Iodine I 131 MOAB 8H9

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.

Outcome Measures

Primary Outcome Measures

Number of patients that have treatment related toxicities [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts 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.