Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00424489
• Date of registration: 18/01/2007
• Prospective Registration: No
• Primary sponsor: Northwestern University
• Public title: Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis
• Scientific title: Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis
• Date of first enrolment: February 2002
• Target sample size: 9
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00424489
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Richard Burt, MD
• Affiliation: Northwestern University and Northwestern Memorial Hospital

Key inclusion & exclusion criteria

Inclusion Criteria (Patients must fulfill all of the following)

1. Established diagnosis of myasthenia gravis defined as clinical evidence of muscle
weakness and fatigue ability and supported, an abnormal EMG-NCV repetitive nerve
stimulation (or single-fiber EMG) or Lambert-Eaton Myasthenic Syndrome without
evidence of malignancy.

2. Ages 15-65 years.

3. Positive antibody preferred (anti-AchR, MuSK, voltage gated calcium channel,
anti-striational).

4. Failure of thymectomy (except for Lambert-Eaton Myasthenic Syndrome).

5. Failure anticholinesterase therapy, corticosteroids, and at least two of the
following: azathioprine, cyclosporin, CellCept, cyclophosphamide, plasma exchange, or
IVIG. Failure is defined as at least 6 months of the above drug therapy and an
Osserman score of IIB, III, or IV and not clinically improving.

And at least one of the following:

1. History of myasthenia crises (requiring mechanical ventilation) despite thymectomy and
immunosuppressive therapy.

2. Hospitalized or on ventilator support for myasthenia gravis within the last 18 months
despite thymectomy and immunosuppressive therapy.

3. Inability to maintain nutrition due to muscle weakness.

4. A Karnofsky performance status of 70% or less (may or may not be able to care for
self, but unable to carry on normal activity or unable to do active work).

Exclusion Criteria

1. Significant end organ damage such as:

1. LVEF <40% or deterioration of LVEF during exercise test on MUGA or
echocardiogram.

2. Untreated life-threatening arrhythmia, active ischemic heart disease or heart
failure.

3. DLCO < 40% of predicted value.

4. Serum creatinine > 2.5 mg/dl.

5. Liver cirrhosis, transaminases >3x of normal limits, or bilirubin >2.0 unless due
to Gilberts disease.

2. HIV positive.

3. Uncontrolled diabetes mellitus, or any other illness that in the opinion of the
investigators would jeopardize the ability of the patient to tolerate aggressive
treatment.

4. Prior history of malignancy except localized basal cell or squamous skin cancer. Other
malignancies for which the patient is judged to be cured by local surgical therapy,
such as (but not limited to) head and neck cancer, or stage I or II breast cancer,
will be considered on an individual basis.

5. Positive pregnancy test, inability or unable to pursue effective means of birth
control, failure to willingly accept or comprehend irreversible sterility as a side
effect of therapy.

6. Psychiatric illness or mental deficiency making compliance with treatment or informed
consent impossible.

7. Inability to give informed consent

8. Congenital myasthenia gravis

9. Neonatal myasthenia gravis

10. Osserman grade 1 or 2

11. Pure red cell aplasia

12. Any patient on insulin



Age minimum: 15 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myasthenia Gravis

Intervention(s)

Drug: ATG (rabbit)

Drug: Cyclophosphamide

Biological: Hematopoietic Stem Cell Transplantation

Drug: G-CSF

Drug: Methylprednisolone

Drug: Mesna

Primary Outcome(s)

Survival [Time Frame: Up to 5 years]

Secondary ID(s)

Myasthenia Gravis Auto 2002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/08/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00424489