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Closed early due to low accrual.
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rituximab | Other | Single Arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-CD20 (Rituximab) | Drug | 4 weekly doses of IV rituxan at 375 mg/m2 on days 1, 8, 15 and 22 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Individuals were followed for adverse events until day 270 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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 -
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Jean M Tersak, M.D. | Children's Hospital of Pittsburgh Department of Hematology Oncology and BMT | Principal Investigator |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rituximab | Participants received 4 weekly doses of IV rituxan at 375 mg/m^2 on days 1, 8, 15 and 22 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rituximab | Participants received 4 weekly doses of IV rituxan at 375 mg/m^2 on days 1, 8, 15 and 22 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 4 weeks |
|
In addition to outlined in-office evaluations, telephone contact to inquire regarding hospitalizations and adverse event questioning will be performed at days 60, 120 and 270 due to the length of time between scheduled testing.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rituximab | Participants received 4 weekly doses of IV rituxan at 375 mg/m^2 on days 1, 8, 15 and 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile illness with upper respiratory symptoms and dehydration | General disorders | Non-systematic Assessment | Patient was admitted for community acquired febrile illness with upper respiratory symptoms and dehydration. Blood cultures were negative. Patient recovered and was discharged to home two days following admission. Event was unrelated to study drug. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jean M. Tersak, M.D. | UPMC Children's Hospital of Pittsburgh | 412-692-8570 | jean.tersak@chp.edu |
| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| D053578 | Opsoclonus-Myoclonus Syndrome |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| 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. | 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. | 2 years |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Region of Enrollment | Number | participants |
|
| 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. | Mean | Full Range | units on a scale |
|
Participants received 4 weekly doses of IV rituxan at 375 mg/m^2 on days 1, 8, 15 and 22
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Individuals were followed for adverse events until day 270 |
|
|
|
| Secondary | 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. | Posted | Mean | Full Range | score on a scale | Baseline, following the four infusions, at months 3, 6, 12, 18 and 24 following the first infusion. |
|
|
|
| Secondary | Human-anti-chimeric Antibody (HACA) Development | Blood samples to be evaluated for the occurrence of antibody formation and potential effect on pharmacokinetic profiles. | These studies were unable to be performed due to withdraw of funding from the study sponsor. 0 of 4 patients participated. | Posted | Baseline; 3, 6, 9 months post treatment |
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 2 years |
|
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|
| 1 |
| 4 |
| 0 |
| 4 |
|
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| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D010257 | Paraneoplastic Syndromes |
| D015835 | Ocular Motility Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003389 | Cranial Nerve Diseases |
| D019636 | Neurodegenerative Diseases |
| D009207 | Myoclonus |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D005128 | Eye Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |