NeuroblastomaPhase 2NCT00202930
Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
A Phase 2 study testing anti-CD20 (Rituximab) in people with Neuroblastoma and Opsoclonus-myoclonus, run by Jean M. Tersak, M.D..
Trial summary
The purpose of this study is to evaluate the feasibility of giving four weekly doses of Rituximab (anti-CD20 antibody) in the treatment of children with refractory neuroblastoma associated opsoclonus-myoclonus. Read more about this study
- Who is it for?
- Ages 2 months to 18 years
- Conditions the study is for
- Neuroblastoma, Opsoclonus-myoclonus
- What is being tested?
- anti-CD20 (Rituximab)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- No sites listed yet
- Study dates
- Jul 2005to 5 Feb 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 2 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pathologic confirmation of diagnosis of neuroblastoma Surgical resection of primary tumor Symptoms of OMS despite a minimum of one month of steroid therapy Must meet all laboratory criteria to demonstrate adequate organ function -
Who cannot join
- Patients currently receiving systemic chemotherapy for treatment of neuroblastoma Patients with documented active infection Patients who are HIV, Hep B or Hep C positive Organ toxicity from any prior therapy or surgical intervention must be resolved prior to study entry
- -
About this study
The purpose of this study is to evaluate the feasibility of giving four weekly doses of Rituximab (anti-CD20 antibody) in the treatment of children with refractory neuroblastoma associated opsoclonus-myoclonus. Patients must have continued symptoms of opsoclonus, myoclonus and or ataxia despite surgical resection and a minimum of one month of steroid therapy. Evaluations include clinical symptoms of opsoclonus-myoclonus and ataxia as well as detailed evaluation of learning and development.
Read the detailed description
Opsoclonus-myoclonus ataxia syndrome (OMS) is a rare immune mediated paraneoplastic syndrome that occurs in approximately 2 to 3% of children with neuroblastoma. Children with neuroblastoma associated opsoclonus-myoclonus tend to have a favorable prognosis from the standpoint of the cure of their cancer. Unfortunately,approximately two-thirds of this subgroup of patients are left with long term sequellae of the syndrome, including residual symptoms of opsoclonus, myoclonus, ataxia, learning difficulties and disturbance of sleep and mood.
Multiple lines of evidence indicate an immune mechanism to this rare disorder. This includes occurence of OMS in the post-infectious state, aggressive lymphocytic infiltration of the tumor in children with OMS, and documented responses to therapries that act through suppression of the immune system.
The current study utilizes four weekly doses of anti-CD 20 antibody (rituximab) to treat children with refractory OMS. Refractory disease is defined as continued symptoms of OMS despite surgical resection of the tumor and a minimum of one month of steroid therapy.
All patients have baseline OMS evaluation and detailed neurocognitive testing with all studies being repeated at the completion of the four weekly infusions. OMS testing is repeated at Month 3. OMS testing and detailed neurocognitive testing is conducted at 6 months intervals until 2 years from the initial infusion.
The goal of the study is to utilize this novel therapy to improve long term neurologic and neurodevelopmental outcome in children with refratory neuroblastoma associated opsoclonus-myoclonus.
- Conditions
- Neuroblastoma, Opsoclonus-myoclonus
- Being tested
- anti-CD20 (Rituximab)
- Keywords
- neuroblastoma, Opsoclonus-myoclonus, rituximab
- Medical subject headings
- Neuroblastoma, Opsoclonus-Myoclonus Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD20 (Rituximab)Drug
Also called Rituxan
4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Other | Single Arm Receives: Drug: anti-CD20 (Rituximab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of Using 4 Weekly Rituximab Infusions
To evaluate the feasibility of using 4 weekly Rituximab infusions in the treatment of children with neuroblastoma associated opsoclonus-myoclonus syndrome (OMS). The first infusion involved a slow up titration from an initial rate of 0.5 mg/kg/hour to a maximum of 400 mg/hour. If well tolerated, the subsequent infusions were administered at a starting rate of 1 mg/kg/hour to a maximum of 100 mg/hour for the first hour. In the absence of adverse reaction doses were escalated by 1 mg/kg/hour (maximum 100 mg increase per hour) every 30 minutes to a maximum rate of 400 mg/hour. If hypersensitivity or infusion related events occurred, the infusion was temporarily interrupted and resumed at 50% of the previous rate if reaction resolves. The number of participants for whom the study dosing was feasible is reported.
Measured: 4 weeks
Toxicity of Rituximab
The trial was to be terminated early for any grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death. The number of participants who experienced these events [grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death] is reported.
Measured: Individuals were followed for adverse events until day 270
Secondary outcomes (3)
OMS Evaluation Scale of Motor-Performance
OMS Evaluation Scale of Motor-Performance This scoring system utilizes a scale of 0 to 3, with 0 being unaffected by OMS, and 3 representing those with severe impairment. OMS testing will be scored by two independent scorers who have special expertise in the evaluation and management of children with neurologic disorders. The mean of these scores will be obtained, and a standard error of the mean reported.
Measured: Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
Human-anti-chimeric Antibody (HACA) Development
Blood samples to be evaluated for the occurrence of antibody formation and potential effect on pharmacokinetic profiles.
Measured: Baseline; 3, 6, 9 months post treatment
Peripheral B Cell Depletion
B cell depletion was measured through analysis of serum IgG levels. The number of participants who experienced B cell depletion is reported.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJul 2005
- Primary completionDec 2008
- Study completion5 Feb 2009
Why it stopped: Closed early due to low accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeuroblastomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jean M. Tersak, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, Jean M. Tersak, M.D., University of Pittsburgh
- Investigators
- Jean M Tersak, M.D., Principal investigator, Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202930
- Sponsor's protocol ID
- IRB0405652
- Status last verified
- Jan 2021
- First submitted
- 12 Sep 2005
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Rituximab in Opsoclonus-Myoclonus in Children With Neuroblastoma
- ClinicalTrials.gov ID
- NCT00202930
- Acronym / sponsor ID
- IRB0405652
- Conditions
- Neuroblastoma, Opsoclonus-myoclonus
- Keywords
- neuroblastoma, Opsoclonus-myoclonus, rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed early due to low accrual.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Jean M. Tersak, M.D.University, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jul 2005
- Primary completion
- Dec 2008 (actual)
- Study completion
- 5 Feb 2009 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 22 Jan 2021
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 evaluate the feasibility of giving four weekly doses of Rituximab (anti-CD20 antibody) in the treatment of children with refractory neuroblastoma associated opsoclonus-myoclonus. Patients must have continued symptoms of opsoclonus, myoclonus and or ataxia despite surgical resection and a minimum of one month of steroid therapy. Evaluations include clinical symptoms of opsoclonus-myoclonus and ataxia as well as detailed evaluation of learning and development.
Detailed description
Opsoclonus-myoclonus ataxia syndrome (OMS) is a rare immune mediated paraneoplastic syndrome that occurs in approximately 2 to 3% of children with neuroblastoma. Children with neuroblastoma associated opsoclonus-myoclonus tend to have a favorable prognosis from the standpoint of the cure of their cancer. Unfortunately,approximately two-thirds of this subgroup of patients are left with long term sequellae of the syndrome, including residual symptoms of opsoclonus, myoclonus, ataxia, learning difficulties and disturbance of sleep and mood.
Multiple lines of evidence indicate an immune mechanism to this rare disorder. This includes occurence of OMS in the post-infectious state, aggressive lymphocytic infiltration of the tumor in children with OMS, and documented responses to therapries that act through suppression of the immune system.
The current study utilizes four weekly doses of anti-CD 20 antibody (rituximab) to treat children with refractory OMS. Refractory disease is defined as continued symptoms of OMS despite surgical resection of the tumor and a minimum of one month of steroid therapy.
All patients have baseline OMS evaluation and detailed neurocognitive testing with all studies being repeated at the completion of the four weekly infusions. OMS testing is repeated at Month 3. OMS testing and detailed neurocognitive testing is conducted at 6 months intervals until 2 years from the initial infusion.
The goal of the study is to utilize this novel therapy to improve long term neurologic and neurodevelopmental outcome in children with refratory neuroblastoma associated opsoclonus-myoclonus.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Other | Drug: anti-CD20 (Rituximab)Single Arm |
Who may qualify
- Ages
- 2 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Pathologic confirmation of diagnosis of neuroblastoma Surgical resection of primary tumor Symptoms of OMS despite a minimum of one month of steroid therapy Must meet all laboratory criteria to demonstrate adequate organ function -
Key exclusion criteria (2 listed)
- Patients currently receiving systemic chemotherapy for treatment of neuroblastoma Patients with documented active infection Patients who are HIV, Hep B or Hep C positive Organ toxicity from any prior therapy or surgical intervention must be resolved prior to study entry
- -
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 |
|---|---|---|
| anti-CD20 (Rituximab)Also: Rituxan4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22 | Drug | Rituximab |
Primary outcome
Feasibility of Using 4 Weekly Rituximab Infusions
Time frame: 4 weeks
To evaluate the feasibility of using 4 weekly Rituximab infusions in the treatment of children with neuroblastoma associated opsoclonus-myoclonus syndrome (OMS). The first infusion involved a slow up titration from an initial rate of 0.5 mg/kg/hour to a maximum of 400 mg/hour. If well tolerated, the subsequent infusions were administered at a starting rate of 1 mg/kg/hour to a maximum of 100 mg/hour for the first hour. In the absence of adverse reaction doses were escalated by 1 mg/kg/hour (maximum 100 mg increase per hour) every 30 minutes to a maximum rate of 400 mg/hour. If hypersensitivity or infusion related events occurred, the infusion was temporarily interrupted and resumed at 50% of the previous rate if reaction resolves. The number of participants for whom the study dosing was feasible is reported.
Toxicity of Rituximab
Time frame: Individuals were followed for adverse events until day 270
The trial was to be terminated early for any grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death. The number of participants who experienced these events [grade 3 or 4 toxicity that did not resolve in 2 of the first 5 patients treated, or for any infusion related death] is reported.
3 secondary outcomes
OMS Evaluation Scale of Motor-Performance
Time frame: Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion.
Human-anti-chimeric Antibody (HACA) Development
Time frame: Baseline; 3, 6, 9 months post treatment
Peripheral B Cell Depletion
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jean M Tersak, M.D. principal investigator
Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing anti-CD20 (Rituximab) in people with Neuroblastoma and Opsoclonus-myoclonus, run by Jean M. Tersak, M.D..
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 1 inclusion and 2 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: stopped early, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Feasibility of Using 4 Weekly Rituximab Infusions (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jan 2021.