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

Y-mAbs Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Sarcoma; Neuroblastoma; Brain and Central Nervous System Tumors

Treatments: Drug: Iodine I 131 MOAB 8H9

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00089245

MSKCC-03133

03-133

Details and patient eligibility

About

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.

Full 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.

Enrollment: 177 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

177 participants in 1 patient group

Radiolabeled Monoclonal Antibody Therapy

Experimental group

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.

Treatment:

Drug: Iodine I 131 MOAB 8H9

Drug: Iodine I 131 MOAB 8H9