Hematopoietic Stem Cell Transplant in Devic's Disease

NCT00787722 | Completed Phase 1 Results FDA Drug

• 1 other identifier: DIAD Devic's Disease Auto 2008
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to examine whether treating Devic's disease patients with high dose cyclophosphamide together with rabbit antithymocyte globulin (rATG)/rituximab (drugs which reduce the function of the immune system), followed by return of previously collected patient's stem cells will result in improvement in Devic's disease. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the intense chemotherapy is to destroy the cells in patient's immune system, which may be causing his/her disease. The purpose of the stem cell infusion is to produce a normal immune system that will no longer attack patient's body. The purpose of study is to examine the safety and efficacy of this treatment. The drugs used in this study treatment are drugs for commonly used for immune suppression.

Conditions

Devic's Disease

Keywords

High dose immunosuppressive therapy; Hematopoietic stem cell support

Outcome Measures

Primary Outcomes (1)

• Survival

  survival rate will be evaluated at 6 months,1 year, 2 year, 3 year, 4 year, 5 year after the transplant

  6 months, 1 year, 2 year, 3 year, 4 year, 5 year - after the transplant

Secondary Outcomes (5)

• Quality of Life (QOL) Short Form - 36 (SF-36)

  pre-transplant 12mo and 5 years

• Post HSCT Immune -Modulating Medication and Relapse

  Pre transplant and 6 months, 1 year, 2 year, 3 year, 4 year and 5 year after transplant

• Number of Patients Who Require No Device Assistance for Ambulation

  6 months, 1 year, 2 year, 3 year, 4 year, 5 year - after the transplant

• Disability Score: Expanded Disability Status Scale (EDSS)

  pretransplant 6 month, 5 year

• NMO-IgG Aquaporin- 4 Autoantibody Titer

  Pretransplant and 5 year Post Transplant

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

Hematopoietic stem cell transplantation will be performed after conditioning regimen of cyclophosphamide, G-CSF, Mesna, rATG, rituximab, and methylprednisolone.

Procedure: Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: G-CSF; Drug: rATG; Drug: Mesna; Drug: Rituximab; Drug: Methylprednisolone

Interventions

Hematopoietic Stem Cell Transplantation PROCEDURE

Infusion of participant's own stem cells

Hematopoietic Stem Cell Transplantation

Cyclophosphamide DRUG

A medication used as chemotherapy and to suppress the immune system

Also known as: Cytoxan, Neosar

Hematopoietic Stem Cell Transplantation

G-CSF DRUG

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Also known as: Neupogen, Filgrastim, Granix, Zarxio

Hematopoietic Stem Cell Transplantation

rATG DRUG

A rabbit polyclonal antibody to lymphocytes

Also known as: Thymoglobulin, Anti-Thymocyte Globulin

Hematopoietic Stem Cell Transplantation

Mesna DRUG

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

Also known as: Mesnex

Hematopoietic Stem Cell Transplantation

Rituximab DRUG

Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer

Also known as: Rituxan

Hematopoietic Stem Cell Transplantation

Methylprednisolone DRUG

A corticosteroid medication used to suppress the immune system and decrease inflammation

Also known as: Solu-Medrol, Depo-Medrol

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 16-65, at the time of pretransplant evaluation
• An established diagnosis of Devic's disease (more than one acute attack)
• NMO- IgG aquaporin-4 autoantibody positive

You may not qualify if:

• Paraplegia or quadriplegia and legal blindness (defined as visual acuity of 20/200 or less in the better eye with the best correction possible)
• Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy
• Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis
• Positive pregnancy test
• Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
• forced expiratory volume at one (FEV1) / forced vital capacity (FVC) \< 60% of predicted after bronchodilator therapy (if necessary)
• Diffusing capacity of lung for carbon monoxide (DLCO) \< 50% of predicted
• Resting left ventricular ejection fraction (LVEF) \< 50 %
• Serum creatinine \> 2.0 mg/dl
• Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins
• Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams
• Bilirubin \> 2.0 mg/dl
• Platelet count \< 100,000/ul or absolute neutrophil count (ANC) \< 1000/ul
• Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Burt RK, Balabanov R, Han X, Burns C, Gastala J, Jovanovic B, Helenowski I, Jitprapaikulsan J, Fryer JP, Pittock SJ. Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica. Neurology. 2019 Oct 29;93(18):e1732-e1741. doi: 10.1212/WNL.0000000000008394. Epub 2019 Oct 2.

  PMID: 31578302 BACKGROUND

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Filgrastim; thymoglobulin; Antilymphocyte Serum; Mesna; Rituximab; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye 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; 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; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Kathleen Quigley
• Organization: Northwestern University

k-quigley@northwestern.edu

312-695-8192

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

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: October 31, 2008
• First Posted: November 7, 2008
• Study Start: October 10, 2009
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)