Effectiveness of Rituximab in Pediatric OMS Patients.

NCT00244361 | Completed Phase 1 DMC

• 2 other identifiers: IND #11,771SCRIHS (04-112)
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to reduce the symptoms of OMS by testing rituximab (Rituxan®), to remove B lymphocytes that make antibodies and trigger brain inflammation. Evidence suggests that autoimmune brain inflammation causes the symptoms of OMS. This study of blood and spinal fluid intends to find out what effect rituximab has on OMS and on the spinal fluid B-cells. Rituximab targets and destroys B-cells, which make antibodies that can attack the brain and cause may OMS. It is infused through a vein over a period of several hours. Rituximab has been used widely and studied extensively since its approval in 1997 by the U.S. Food and Drug Administration (FDA) for non-Hodgkin's B-cell Lymphoma (NHL). Today, more than 300,000 patients have received rituximab, and it is part of more than 200 completed, ongoing, or planned clinical trials. Rituximab is not FDA-approved for OMS.

Conditions

Opsoclonus-myoclonus Syndrome; Opsoclonus; Myoclonus; Ataxia

Keywords

opsoclonus; myoclonus

Outcome Measures

Primary Outcomes (1)

• Determine the effectiveness & selectivity of rituximab at depleting CSF B-cells in OMS with intrathecal B-cell expansion. This requires CSF & blood lympocyte immunophenotyping prior to the first infusion & intervals for 1 year after the final infusion.

Secondary Outcomes (1)

• Evaluate the clinical efficacy & safety of rituximab by clinical assessments, scoring of videotapes for neurological severity, and various blood tests prior to the first infusion and then at one, three, six, and twelve months post the final infusion.

Interventions

rituximab DRUG

Eligibility Criteria

• Age: 6 Months - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• written consent from parents
• have symptomatic OMS
• have CSF B-cell expansion (\>1% B-cells)
• adequate renal function as indicated by normal BUN \[10-25 mg/dL\] and creatinine \[0.4-1.2 mg/dL\]
• adequate liver function, as indicated by up to 2x normal AST \[0-35 U/L\] and ALT \[0-35 U/L\].
• men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment

You may not qualify if:

• treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (which ever is longer)
• receipt of a live vaccine within 4 weeks prior to enrollment
• previous treatment with Rituximab
• prior antibody therapy (does not include IVIg) within past 6 months
• history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• history of HIV (patients considered high risk will be screened)
• history of hepatitis B and/or hepatitis C (patients considered high risk will be screened)
• history of recurrent significant infection or history of recurrent bacterial infections
• known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment)
• significant cardiac (symptomatic arrhythmias or symptomatic structural heart disease) or pulmonary disease (including obstructive pulmonary disease)
• concomitant chemotherapy
• hemoglobin: \>13.5 gm/dL or \<10.0 gm/dL
• platelets: \<100,000/mm or \>500,000/mm K/cumm

Sponsors & Collaborators

• National Pediatric Neuroinflammation Organization, Inc.: lead
• Genentech, Inc.: collaborator

Study Sites (1)

National Pediatric Myoclonus Center, Department of Neurology, SIU School of Medicine, 751 N Rutledge St

Springfield, Illinois, 62794, United States

Location

Related Publications (3)

• Pranzatelli MR, Tate ED, Travelstead AL, Verhulst SJ. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS. Cytokine. 2011 Mar;53(3):384-9. doi: 10.1016/j.cyto.2010.12.004. Epub 2011 Jan 5.

  PMID: 21211990 DERIVED

• Pranzatelli MR, Tate ED, Verhulst SJ, Bertolone SJ, Bhatla D, Granger M, Lebowizc J, Lockhart SK, Wiley JM. Pediatric dosing of rituximab revisited: serum concentrations in opsoclonus-myoclonus syndrome. J Pediatr Hematol Oncol. 2010 Jul;32(5):e167-72. doi: 10.1097/MPH.0b013e3181cf0726.

  PMID: 20606544 DERIVED

• Pranzatelli MR, Tate ED, Travelstead AL, Colliver JA. Long-term cerebrospinal fluid and blood lymphocyte dynamics after rituximab for pediatric opsoclonus-myoclonus. J Clin Immunol. 2010 Jan;30(1):106-13. doi: 10.1007/s10875-009-9335-3. Epub 2009 Oct 17.

  PMID: 19838774 DERIVED

MeSH Terms

Conditions

Opsoclonus-Myoclonus Syndrome; Ocular Motility Disorders; Myoclonus; Ataxia

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Central Nervous System Diseases; Nervous System Diseases; Cranial Nerve Diseases; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael R Pranzatelli, M.D.

  National Pediatric Neuroinflammation Organization, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 24, 2005
• First Posted: October 26, 2005
• Study Start: June 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: May 10, 2011

Record last verified: 2011-05

Locations

US (1)