NCT02282514

Stem Cell Transplantation for Stiff Person Syndrome (SPS)

Non-myeloablative Hematopoietic Stem Cell Transplantation for Stiff Person Syndrome (SPS) and Anti-GAD Antibody Variants: Progressive Encephalomyelitis With Rigidity and Myoclonus (PERM), and Adult Onset Autoimmune Anti-GAD Positive Cerebellar Ataxia

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Non-myeloablative regimens (as the investigators use herein) are designed to maximally suppress the immune system without destruction of the bone marrow stem cell compartment. When using a non-myeloablative regimen recovery occurs without infusion of stem cells and the stem cells are autologous. While not necessary for recovery, stem cell infusion may shorten the interval of neutropenia and attendant complications. Thus in reality there is no transplant only an autologous supportive blood product. Based on our encouraging results of non-myeloablative hematopoietic stem cell transplantation, for patients with multiple sclerosis and chronic inflammatory demyelinating polyneuropathy, the investigators will investigate the role of non-myeloablative hematopoietic stem cell transplantation for patients with SPS who require assistance to ambulate.

Detailed description

Pre-study Testing 1. History and physical 2. Electrocardiogram (EKG) 3. Dobutamine stress echocardiogram 4. High-resolution computed tomography of the chest (HRCT) 5. Blood draw for laboratory tests- these tests will include a complete blood count, evaluating liver and kidney function, assessing immune system, tissue typing, and checking for certain germs that can cause infections, including a pregnancy test for females and prostate-specific antigen (PSA) for male as well as testing for HIV 6. Pulmonary Function Test (PFT) 7. Electromyography (EMG) 8. Magnetic Resonance Imaging (MRI) of the Abdomen and Pelvis 9. Magnetic Resonance Imaging (MRI) of the Spinal Cord 10. Magnetic Resonance Imaging (MRI) of the Brain with Gadolinium (only if PERM of cerebellar ataxia) 11. Colonoscopy 12. Mammogram (if female) 13. Timed ambulation 14. Quality of Life Questionnaires \[ Short Form (36) Health Survey (SF36) and Barthel Index\] 15. Chronic Pain Acceptance Questionnaire (CPAQ) 16. Rankin Functional Scale 17. Modified Ashworth Scale 18. Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1), Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2) antibody (only if cerebellar ataxia) 19. Spinocerebellar ataxia (SCA) 1, 2, 3, 4, 5, 6, 7, 8 genes (only if ataxia) Study Treatment Stem Cell Collection: Cyclophosphamide 2.0 gm/m2 will be given on day 0, G-CSF 5-10 mcg/kg/day subcutaneous (SQ) will start on day +5 and will continue until apheresis is discontinued. Apheresis will begin when the absolute neutrophil count (ANC) \> 1.0 x 109/L and continue until \>2.0 x 106 cluster of differentiation 34 (CD34)+ cells/kg patient weight are cryopreserved. A 10-15 liter apheresis will be performed unless stopped earlier for clinical judgment of toxicity (e.g., numbness, tetany). A maximum of four apheresis will be performed.

Conditions

• Stiff-Person Syndrome

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Hematopoietic Stem Cells	The stem cells will be collected from patient's blood during mobilization. Then the patient will be given high dose chemotherapy in accordance with approved recommendations for use in conditioning regimens for stem cell transplant in autoimmune diseases. Autologous Hematopoietic Stem Cell Transplantation is to re-infuse immature cells that can re-establish blood production and patient's immune system.
DRUG	Cyclophosphamide	An alkylating agent which causes prevention of cell division by forming adducts with DNA
DRUG	Mesna	Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
DRUG	rATG	A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
DRUG	Methylprednisolone	Steroid
DRUG	G-CSF	Granulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
DRUG	Rituxan	A chimeric monoclonal antibody used in the treatment of B cell non-Hodgkin's lymphoma, B cell leukemia, and some autoimmune disorders

Timeline

• Start date: 2014-10-01
• Primary completion: 2019-08-19
• Completion: 2019-08-30
• First posted: 2014-11-04
• Last updated: 2021-01-27
• Results posted: 2021-01-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study