Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )

Johns Hopkins University

Status: Withdrawn

Conditions: ROHHAD Syndrome

Treatments: Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02441491

IRB00060912

J1520 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 12 months to 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

0 participants in 1 patient group

Cyclophosphamide

Experimental group

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.

Treatment:

Drug: Cyclophosphamide