Clinical trial NCT02441491: 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
Overall status: WITHDRAWN
Phase: NA
Conditions: ROHHAD Syndrome
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2015-05-12
Enrollment: 0
Sex: ALL
Minimum age (years): 12
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
timeFrame: 18 months
measure: 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.
timeFrame: 18 months
Secondary outcomes:
measure: To calculate Area Under Curve (AUC) of high dose cyclophosphamide in obese children.
timeFrame: predose, 0, 1, 2, 4, 8, 12 and 24 hrs from the completion of infusion.
measure: 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.
timeFrame: 18 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Cancer Center
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Allen Chen, MD, PhD
role: STUDY_CHAIR
References:
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.