Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
Primary Purpose
ROHHAD Syndrome
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for ROHHAD Syndrome
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of ROHHAD syndrome confirmed by two physicians.
- Any symptomatic improvement in response to a course of rituximab (five weekly doses) as assessed by parents and/or treating physician
- Normal brain MRI
- Cared for at home by the family
- Patients requiring bilevel positive airway pressure (BiPAP) support are eligible
- Negative pregnancy test for post pubertal female patients
Exclusion Criteria:
- Cardiac ejection fraction <40% or shortening fraction <20%.
- Inadequate pulmonary function, i.e. forced vital capacity or forced expiratory volume at one second < 50% of predicted for children greater than 8 years of age, or oxygen saturation <93% on pulse oximetry for younger children.
- Ventilator dependent
- Known chromosomal abnormality
- Active cancer diagnosis. Neuroblastoma that requires only follow up is eligible.
- Pregnancy
Sites / Locations
- Sidney Kimmel Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide
Arm Description
Cyclophosphamide will be given by vein once a day for four straight days. Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, will be given by vein once every day to try to help your blood cells grow faster.
Outcomes
Primary Outcome Measures
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
Safety and toxicity of high-dose cyclophosphamide used to treat children with ROHHAD of as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Secondary Outcome Measures
To calculate Area Under Curve (AUC) of high dose cyclophosphamide in obese children.
Neuropsychological function of patients with ROHHAD before and after high-dose cyclophosphamide measured using complementary age appropriate evaluation tools including Wechsler Preschool and Primary Scale of Intelligence RAN objects, and AIM.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02441491
Brief Title
Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
Official Title
High-dose Cyclophosphamide for the Treatment of ROHHAD (Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation) Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
ROHHAD (rapid onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation) syndrome is a rare pediatric disorder associated with a cancer called neuroblastoma and presumed to be driven by an attack of the immune system on specific area in the brain. Patients develop severe symptoms and often succumb to this disease. Based on the researchers' experience the investigators conduct a clinical trial to study intensive immunosuppression with high-dose cyclophosphamide in these patients. In addition to describing the symptomatic improvement, the investigators' trial seeks to define objective markers of disease activity.
Detailed Description
Baseline evaluation will include:
Sleep study and pulmonary evaluation Hormone levels Determination of up to 6 key ROHHAD-related symptoms to be followed Hyperphagia questionnaire 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) positron emission tomography (PET) scan Dual energy x-ray absorptiometry (DXA) scan Cerebrospinal fluid (CSF) analysis
Patients will be treated with cyclophosphamide, 50 mg/kg (ideal body weight)/dose daily for 4 days, with Mesna and hydration as prophylaxis against hemorrhagic cystitis. Supportive care will include mucosal care, transfusions, infection prophylaxis, and empiric treatment for febrile neutropenia.
Composite severity score will be assessed to measure response of key symptoms, and formal neuropsychological testing, sleep study, and hormone studies will be performed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ROHHAD Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide
Arm Type
Experimental
Arm Description
Cyclophosphamide will be given by vein once a day for four straight days.
Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, will be given by vein once every day to try to help your blood cells grow faster.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Cyclophosphamide will be given by vein once a day for four straight days.
Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, by vein once every day to try to help your blood cells grow faster.
Primary Outcome Measure Information:
Title
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
Time Frame
18 months
Title
Safety and toxicity of high-dose cyclophosphamide used to treat children with ROHHAD of as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
To calculate Area Under Curve (AUC) of high dose cyclophosphamide in obese children.
Time Frame
predose, 0, 1, 2, 4, 8, 12 and 24 hrs from the completion of infusion.
Title
Neuropsychological function of patients with ROHHAD before and after high-dose cyclophosphamide measured using complementary age appropriate evaluation tools including Wechsler Preschool and Primary Scale of Intelligence RAN objects, and AIM.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of ROHHAD syndrome confirmed by two physicians.
Any symptomatic improvement in response to a course of rituximab (five weekly doses) as assessed by parents and/or treating physician
Normal brain MRI
Cared for at home by the family
Patients requiring bilevel positive airway pressure (BiPAP) support are eligible
Negative pregnancy test for post pubertal female patients
Exclusion Criteria:
Cardiac ejection fraction <40% or shortening fraction <20%.
Inadequate pulmonary function, i.e. forced vital capacity or forced expiratory volume at one second < 50% of predicted for children greater than 8 years of age, or oxygen saturation <93% on pulse oximetry for younger children.
Ventilator dependent
Known chromosomal abnormality
Active cancer diagnosis. Neuroblastoma that requires only follow up is eligible.
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allen Chen, MD, PhD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27313069
Citation
Jacobson LA, Rane S, McReynolds LJ, Steppan DA, Chen AR, Paz-Priel I. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide. Pediatrics. 2016 Jul;138(1):e20151080. doi: 10.1542/peds.2015-1080. Epub 2016 Jun 16.
Results Reference
derived
Learn more about this trial
Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
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