Neoplasms

Nervous System Diseases

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Symptoms and General Pathology

Rare Diseases

Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Cyclophosphamide

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Autologous Hematopoietic Stem Cell Transplantation will be performed after conditioning

Autologous Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

ATG (rabbit)

G-CSF

Richard Burt, MD

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.

There will be no randomization in this study. All subjects who are determined to be eligible for the study treatment will receive high dose cyclophosphamide and ATG followed by infusion of autologous peripheral blood stem cells. The procedures the subject will undergo are as follows:

1. Physician visit to determine potential eligibility for the study. Subjects will be evaluated by a transplant physician and a neurologist. They will have a complete physical examination and will provide a full medical history at these visits. The study will be described in detail by the transplant physician and nurse and the consent form will be provided to be taken home to read.
2. Insurance verification. Subjects who remain interested in pursuing the study treatment and who have refractory myasthenia gravis will proceed to the insurance verification phase. Third party payment or self-pay must be verified before subjects can proceed.
3. Consent form. Prior to proceeding, the appropriate signatures will be obtained on the consent form. Subjects will be given an opportunity to ask further questions of the attending physician and transplant nurse prior to signing the consent form.
4. Pre-transplant testing. To determine final eligibility for the study, subjects will undergo a series of tests/procedures. These include: CXR; electrocardiogram; MUGA or echocardiogram; pulmonary function test; CT scan of the sinuses; CT scan of the chest to r/o thymoma; dental examination; urinalysis; and blood testing to include CBC, chemistries, liver and kidney function tests, coagulation studies, viral studies and, for females, a pregnancy test. All pre-transplant testing is routine medical testing done to verify diagnosis and to insure adequate organ function and absence of viral illnesses which would preclude a safe transplant course.
5. Autologous peripheral blood stem cell collection. Subjects who are proceeding to transplant will undergo a routine procedure for the mobilization and collection of peripheral blood stem cells. This includes the administration of IV cyclophosphamide, given as an inpatient requiring an overnight stay, followed by the subcutaneous administration of G-CSF, to be self-administered as an outpatient. Approximately ten days after the administration of IV cyclophosphamide, the peripheral blood stem cells will be collected as an outpatient in the Blood Center. A pheresis catheter will be placed for this purpose on the first day of leukopheresis. Leukopheresis will be continued on a daily basis until an adequate number of peripheral blood stem cells have been collected (a maximum of four leukophereses may be performed). G-CSF will continue to be administered until leukopheresis is completed. The pheresis catheter will be discontinued when stem cell harvesting is completed. Processed cells will be frozen and stored until they are reinfused after the conditioning regimen.
6. PICC line placement. Subjects will have a double lumen PICC line placed prior to the administration of study treatment for the administration of chemotherapy, IV fluids, blood products and the withdrawal of blood samples. The placement of a PICC line is a routine medical procedure.
7. Study treatment. Subjects will undergo conditioning which will include four days of intravenous high dose cyclophosphamide and three days of intravenous anti-thymocyte globulin (ATG). Both cyclophosphamide and ATG are common immune suppressive agents. The previously collected peripheral blood stem cells will be reinfused following the completion of the conditioning regimen.
8. Post-treatment follow-up. Subjects will have a history and physical by the transplant physician and neurologist at 3 months, 6 months, 12 months, and yearly for 5 years. In addition, routine urinalysis and blood testing will be performed at these same intervals to include CBC, chemistries, kidney and liver function tests.

Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis

Northwestern University

Autologous Hematopoietic Stem Cell Transplantation will be performed after conditioning

Hematopoietic Stem Cell Transplantation: Autologous Hematopoietic Stem Cell Transplantation

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Richard Burt

Survival both treatment related and non-treatment related

Survival

Overall Study

Rituximab

Antineoplastic Agents, Immunological

Four weekly IV infusions of Rituxan with dosage individually calculated per subject.

Rituximab (Rituxan)

Rup Tandan, MD, FRCP

Myasthenia gravis is a disease that happens because the immune system attacks the nervous system. The damage is caused by antibodies produced by B lymphocytes. These antibodies damage a special part of the muscle that helps transmit impulses from nerves to muscles to allow muscles to work properly. This damage results in symptoms of myasthenia gravis. Participants are being asked to participate in this research study because their myasthenia gravis has either failed to respond to treatments commonly used in the disease, or they have had bad side-effects from such treatments.

This is a research study of a drug called Rituximab. Rituximab, also called Rituxan, is a mouse antibody that has been changed to make it similar to a human antibody. Antibodies are proteins that can protect the body from foreign invaders, such as bacteria and viruses, by binding to substances called antigens. Rituxan works by binding to a protein, called the CD20 protein. Rituxan helps to destroy white blood cells that produce antibodies in the body, called B-lymphocytes. It is a treatment given through a vein in the participant's arm over a period of approximately 4-6 hours. It has been approved by the Food and Drug Administration (FDA) for use in patients with a form of cancer of the lymph glands called Non-Hodgkin's Lymphoma (NHL). Rituximab is not approved for their myasthenia gravis.

Treatment with Rituximab is being tried in this research study because Rituximab decreases B lymphocytes. There is preliminary evidence that Rituximab helps some patients with chronic and otherwise difficult to treat myasthenia gravis.

Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction diagnosed on the basis of clinical, electrophysiological and serological features. Cyclosporine as a disease-modifying therapy has been effective in a controlled study; corticosteroids, immunosuppressive agents such as azathioprine and cyclophosphamide, plasmapheresis and intravenous human immune globulin have shown benefit in uncontrolled trials. There are several drawbacks to currently used medical treatments, including serious and debilitating side-effects, prohibitive costs, and the need for continuous or periodical treatment. Almost 20-25% of patients with MG are unresponsive to commonly used therapies, resulting in significant burden and economic loss. Rituximab is a chimeric anti-CD20 monoclonal antibody which produces a substantial reduction in circulating plasma cells (CD19+) and B cells (CD20+) and provides targeted therapy for B-cell lymphomas. Recently, rituximab has been found to be effective in several antibody-mediated autoimmune processes, including immune thrombocytopenia, autoimmune hemolytic anemia, and IgM-related polyneuropathies. There is preliminary evidence in the literature that treatment of MG patients with rituximab is likely to be of benefit. These observations would strongly suggest that rituximab might benefit refractory MG and needs further study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis	NCT00424489	Myasthenia Grav...	Hematopoietic S... Cyclophosphamid... ATG (rabbit) Mesna Methylprednisol... G-CSF	15 Years - 65 Years	Northwestern University
A Pilot Trial of Rituxan in Refractory Myasthenia Gravis	NCT00619671	Refractory Myas...	Rituximab (Ritu...	18 Years - 80 Years	University of Vermont
Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis	NCT00424489	Myasthenia Grav...	Hematopoietic S... Cyclophosphamid... ATG (rabbit) Mesna Methylprednisol... G-CSF	15 Years - 65 Years	Northwestern University
Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis	NCT00424489	Myasthenia Grav...	Hematopoietic S... Cyclophosphamid... ATG (rabbit) Mesna Methylprednisol... G-CSF	15 Years - 65 Years	Northwestern University

Spots Global Cancer Trial Database for refractory myasthenia gravis