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

April 1, 2024 updated by: Johns Hopkins University

High-dose Cyclophosphamide for the Treatment of ROHHAD (Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation) Syndrome

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 22 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cyclophosphamide

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.
Drug: Cyclophosphamide

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.

Other Names:
  • Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
Time Frame: 18 months
18 months
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
18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
predose, 0, 1, 2, 4, 8, 12 and 24 hrs from the completion of infusion.
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
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Study Chair: Allen Chen, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

March 31, 2024

Study Completion (Actual)

March 31, 2024

Study Registration Dates

First Submitted

April 8, 2015

First Submitted That Met QC Criteria

May 11, 2015

First Posted (Estimated)

May 12, 2015

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00060912
  • J1520 (Other Identifier: SKCCC)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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