Effectiveness of Rituximab in Pediatric OMS Patients.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00244361

Recruitment Status : Completed

First Posted : October 26, 2005

Last Update Posted : May 10, 2011

Sponsor:

Collaborator:

Genentech, Inc.

Information provided by:

National Pediatric Neuroinflammation Organization, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Opsoclonus-myoclonus Syndrome Opsoclonus Myoclonus Ataxia	Drug: rituximab	Phase 1 Phase 2

Detailed Description:

Opsoclonus-myoclonus syndrome (OMS) is a rare but pervasive, paraneoplastic neurological disorder, purported to be autoantibody-mediated. We demonstrated expansion of B-cells in cerebrospinal fluid (CSF) despite tumor resection, chemotherapy, or conventional immunotherapy. Whether B-cells can be purged from the CSF compartment with benefit to the patient is unknown. Targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy of centrally-mediated paraneoplastic disorders. The objective of this preliminary study is to determine if rituximab, a monoclonal antibody against CD20+ B-cells, reduces or eliminates CSF B-cells in OMS and whether the reduction results in clinical improvement. B lymphocyte subsets and relevant T-cell subsets will be immunophenotyped in the CSF and peripheral blood of children with OMS by four-color dual-laser flow cytometry. Sixteen children with an increased percentage of CSF B-cells will be treated with rituximab 375 mg/m2 IV once weekly for four consecutive weeks and CSF testing will be repeated at six months with more frequent clinical evaluations and blood testing out to 12 months. Clinical outcome will be rated blindly from videotapes by an experienced observer using a validated 12-item motor evaluation scale and quantifiable parameters of sleep, behavior and motor function. Immunological outcome variables will include percentages of B-cell subsets and quantitative immunoglobulins. Post-treatment results will be compared to pre-treatment values statistically. If rituximab proves to be an efficacious and safe method of treating CSF B-cell expansion and the neurological syndrome, this study will lead to a phase II trial with the eventual aim of gaining FDA approval of rituximab for this indication.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	25 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome
Study Start Date :	June 2005
Actual Primary Completion Date :	December 2007
Actual Study Completion Date :	December 2007

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: VLDLR-associated cerebellar hypoplasia Autosomal recessive cerebellar ataxia type 1

Drug Information available for: Rituximab

Genetic and Rare Diseases Information Center resources: Opsoclonus-myoclonus Syndrome Ocular Motility Disorders Motor Neuro-ophthalmic Disorders

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:	6 Months to 19 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00244361

Locations


United States, Illinois
National Pediatric Myoclonus Center, Department of Neurology, SIU School of Medicine, 751 N Rutledge St
Springfield, Illinois, United States, 62794

Sponsors and Collaborators

National Pediatric Neuroinflammation Organization, Inc.

Genentech, Inc.

Investigators


Principal Investigator:	Michael R Pranzatelli, M.D.	National Pediatric Neuroinflammation Organization, Inc.

More Information

Additional Information:

National Pediatric Myoclonus Center This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.


Responsible Party:	Michael R Pranzatelli, MD, National Pediatric Myoclonus Center/ SIU School of Medicine
ClinicalTrials.gov Identifier:	NCT00244361 History of Changes
Other Study ID Numbers:	IND #11,771 SCRIHS (04-112)
First Posted:	October 26, 2005 Key Record Dates
Last Update Posted:	May 10, 2011
Last Verified:	May 2011

Keywords provided by National Pediatric Neuroinflammation Organization, Inc.:


opsoclonus myoclonus

Additional relevant MeSH terms:


Myoclonus Opsoclonus-Myoclonus Syndrome Syndrome Ocular Motility Disorders Disease Pathologic Processes Dyskinesias Neurologic Manifestations Nervous System Diseases Signs and Symptoms Central Nervous System Diseases Cranial Nerve Diseases	Eye Diseases Paraneoplastic Syndromes, Nervous System Nervous System Neoplasms Neoplasms by Site Neoplasms Paraneoplastic Syndromes Neurodegenerative Diseases Rituximab Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents

To Top