Opsoclonus-myoclonus SyndromePhase 1/2NCT00244361
Effectiveness of Rituximab in Pediatric OMS Patients.
A Phase 1/2 study testing rituximab in people with Opsoclonus-myoclonus Syndrome and Opsoclonus, run by National Pediatric Neuroinflammation Organization, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 19 years
- Conditions the study is for
- Opsoclonus-myoclonus Syndrome, Opsoclonus, Myoclonus
- What is being tested?
- rituximab
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Dec 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Pediatric Myoclonus Center, Department of Neurology, SIU School of Medicine, 751 N Rutledge St
Springfield, Illinois, 62794
About this study
Official title: A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome
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.
Read the 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.
- Conditions
- Opsoclonus-myoclonus Syndrome, Opsoclonus, Myoclonus, Ataxia
- Being tested
- rituximab
- Keywords
- opsoclonus, myoclonus
- Medical subject headings
- Opsoclonus-Myoclonus Syndrome, Ocular Motility Disorders, Myoclonus, Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2005 (estimated)
- Study startJun 2005
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opsoclonus-myoclonus SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Pediatric Neuroinflammation Organization, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Investigators
- Michael R Pranzatelli, M.D., Principal investigator, National Pediatric Neuroinflammation Organization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00244361
- Sponsor's protocol ID
- IND #11,771
- Other IDs
- SCRIHS (04-112)
- Status last verified
- May 2011
- First submitted
- 24 Oct 2005
- Last updated
- 10 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21211990Pranzatelli 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.
PubMed 20606544Pranzatelli 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.
PubMed 19838774
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome
- ClinicalTrials.gov ID
- NCT00244361
- Acronym / sponsor ID
- IND #11,771
- Conditions
- Opsoclonus-myoclonus Syndrome, Opsoclonus, Myoclonus, Ataxia
- Keywords
- opsoclonus, myoclonus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Pediatric Neuroinflammation Organization, Inc.University, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jun 2005
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 26 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 6 months to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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].
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximab | Drug | – |
Primary outcome
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.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2011.
- Derived from this study: PubMed 21211990Pranzatelli 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.
- Derived from this study: PubMed 20606544Pranzatelli 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.
- Derived from this study: PubMed 19838774Pranzatelli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael R Pranzatelli, M.D. principal investigator
National Pediatric Neuroinflammation Organization, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rituximab in people with Opsoclonus-myoclonus Syndrome and Opsoclonus, run by National Pediatric Neuroinflammation Organization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00244361, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2011.