Stem Cell Transplantation for Stiff Person Syndrome (SPS) (SPS)
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|ClinicalTrials.gov Identifier: NCT02282514|
Recruitment Status : Terminated (Could not predict who would respond, relapse or go into remission)
First Posted : November 4, 2014
Results First Posted : January 6, 2021
Last Update Posted : January 27, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Stiff-Person Syndrome||Biological: Autologous Hematopoietic Stem Cells Drug: Cyclophosphamide Drug: Mesna Drug: rATG Drug: Methylprednisolone Drug: G-CSF Drug: Rituxan||Phase 1 Phase 2|
- History and physical
- Electrocardiogram (EKG)
- Dobutamine stress echocardiogram
- High-resolution computed tomography of the chest (HRCT)
- 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
- Pulmonary Function Test (PFT)
- Electromyography (EMG)
- Magnetic Resonance Imaging (MRI) of the Abdomen and Pelvis
- Magnetic Resonance Imaging (MRI) of the Spinal Cord
- Magnetic Resonance Imaging (MRI) of the Brain with Gadolinium (only if PERM of cerebellar ataxia)
- Mammogram (if female)
- Timed ambulation
- Quality of Life Questionnaires [ Short Form (36) Health Survey (SF36) and Barthel Index]
- Chronic Pain Acceptance Questionnaire (CPAQ)
- Rankin Functional Scale
- Modified Ashworth Scale
- Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1), Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2) antibody (only if cerebellar ataxia)
- Spinocerebellar ataxia (SCA) 1, 2, 3, 4, 5, 6, 7, 8 genes (only if ataxia)
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||August 19, 2019|
|Actual Study Completion Date :||August 30, 2019|
Experimental: Hematopoietic Stem Cell Transplantation
The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5, 1.0 mg/kg on days -4 and -3, and then 1.5 mg/kg on days -2 and -1. Methylprednisolone 1000 mg will be infused intravenously before each dose of rATG. Autologous hematopoietic stem cells will be infused intravenously on day 0. A granulocyte-colony stimulating factor (G-CSF) 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment. Intravenous Rituxan (500mg) will be administered on days -6 and +1.
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.
An alkylating agent which causes prevention of cell division by forming adducts with DNA
Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
Other Name: Mesnex
A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Other Name: Thymoglobulin
Other Name: Solu-Medrol
Granulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
A chimeric monoclonal antibody used in the treatment of B cell non-Hodgkin's lymphoma, B cell leukemia, and some autoimmune disorders
Other Name: Rituximab
- Overall Survival [ Time Frame: Mean 3.6 years ]Number of Participants who Did Not Experience Treatment-Related Mortality
- Reduction of Muscle Relaxation Anti-spasmatic Medications [ Time Frame: Mean 3.6 years ]Decrease (50%) and complete discontinuation of muscle relaxation anti-spasmatic medications
- Short-form 36 Quality of Life Questionnaire (SF-36 QOL) [ Time Frame: mean 3.6 years ]Improvement is defined as a statistically significant change in SF-36 QOL score. The scale is 0-100. The lower the score the worse quality of life.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02282514
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Richard Burt, MD||Northwestern University|