Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis

NCT00424489 | Terminated Phase 1 Results

• 1 other identifier: Myasthenia Gravis Auto 2002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myasthenia Gravis

Keywords

Refractory Myasthenia Gravis; Autologous Stem Cell Transplantation; Cyclophosphamide and ATG

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival

  Up to 5 years

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation will be performed after conditioning

Biological: Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: ATG (rabbit); Drug: Mesna; Drug: Methylprednisolone; Drug: G-CSF

Interventions

Hematopoietic Stem Cell Transplantation BIOLOGICAL

Autologous Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Cyclophosphamide DRUG

Also known as: Cytoxan

Hematopoietic Stem Cell Transplantation

ATG (rabbit) DRUG

Hematopoietic Stem Cell Transplantation

Mesna DRUG

Hematopoietic Stem Cell Transplantation

Methylprednisolone DRUG

Hematopoietic Stem Cell Transplantation

G-CSF DRUG

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Ages 15-65 years.
• Positive antibody preferred (anti-AchR, MuSK, voltage gated calcium channel, anti-striational).
• Failure of thymectomy (except for Lambert-Eaton Myasthenic Syndrome).
• 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:
• History of myasthenia crises (requiring mechanical ventilation) despite thymectomy and immunosuppressive therapy.
• Hospitalized or on ventilator support for myasthenia gravis within the last 18 months despite thymectomy and immunosuppressive therapy.
• Inability to maintain nutrition due to muscle weakness.
• 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).

You may not qualify if:

• Significant end organ damage such as:
• LVEF \<40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
• Untreated life-threatening arrhythmia, active ischemic heart disease or heart failure.
• DLCO \< 40% of predicted value.
• Serum creatinine \> 2.5 mg/dl.
• Liver cirrhosis, transaminases \>3x of normal limits, or bilirubin \>2.0 unless due to Gilberts disease.
• HIV positive.
• 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.
• 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.
• 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.
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
• Inability to give informed consent
• Congenital myasthenia gravis
• Neonatal myasthenia gravis
• Osserman grade 1 or 2

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Hematopoietic Stem Cell Transplantation; Cyclophosphamide; thymoglobulin; Mesna; Methylprednisolone; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Small numbers of subjects enrolled

Results Point of Contact

• Title: Dr. Richard Burt
• Organization: Northwestern University

rburt@northwestern.edu

312-695-4960

Study Officials

• Richard Burt, MD

  Northwestern University and Northwestern Memorial Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 18, 2007
• First Posted: January 19, 2007
• Study Start: February 1, 2002
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 31, 2018
• Results First Posted: August 6, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)