Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis

• Status: Terminated
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

MG may be neonatal, congenital, or autoimmune. Neonatal MG arises from transplacental transfer of ACh receptor antibodies from a mother with autoimmune MG to the fetus. Neonatal MG resolves with post delivery clearance of maternal antibodies. Congenital MG results from a genetic defect in the ACh receptor. Patients with congenital MG do not have ACh receptor antibodies. Both neonatal and congenital MG are excluded from this study. Autoimmune MG, which is the most common form of MG, affects approximately 25,000 Americans. Like most autoimmune diseases, it is associated with particular HLA genotypes, has a female predominance, and environmental factors involved in breaking tolerance to the ACh receptor are unknown. Patients with refractory and severe autoimmune MG will be considered candidates for this study.

The purpose of this study is to assess the toxicity/feasibility (phase I) of autologous hematopoietic stem cell transplantation for refractory myasthenia gravis.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Treatments: Cyclophosphamide; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

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