Hematopoietic Stem Cell Support in Vasculitis

NCT00278512 | Terminated Phase 1 Results

• 1 other identifier: DIAD Vasculitis.Auto2002
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The systemic vasculitis is a wide-ranging group of diseases that are characterized by the presence of blood vessel inflammation (1). Despite this common feature, each type of vasculitis has a unique variety of clinical manifestations that influences its degree of disease severity and ultimately its management. Immunosuppressive therapy forms the foundation of treatment for almost all forms of systemic vasculitis. The systemic necrotizing vasculitis (SNV) are a subset of vasculitis with significant morbidity and mortality (2). The SNV are Wegener's granulomatosis, allergic angiitis and granulomatosis (AAG) (also known as Churg-Strauss syndrome), polyarteritis nodosum (PAN), microscopic polyangiitis (MPA), and overlap syndrome. In spite of modern therapeutic immune suppressive agents, there remains a not inconsequential morbidity and mortality associated with SNV. The current standard therapy for SNV is chronic oral cyclophosphamide (1-3 mg/kg/day) and corticosteroids (3-6). Transplant doses of cyclophosphamide at 200 mg/kg infused over 4 days is the most common worldwide transplant regimen for systemic lupus erythematosus (SLE) (7). Like SLE, SNV are cyclophosphamide responsive disease. We, therefore, propose a trial of high dose cyclophosphamide with anti-thymocyte globulin (ATG) for patients with SNV.

Conditions

Vasculitis

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival

  Up to 5 years

Study Arms (2)

Autologous Stem Cell Transplant

EXPERIMENTAL

Autologous Stem Cell Transplant will be performed on eligible patients

Biological: Autologous Stem Cell Transplant; Biological: Allogeneic Stem Cell Transplant; Drug: Cyclophosphamide; Drug: ATG (rabbit); Drug: G-CSF; Drug: Mesna

Allogeneic Stem Cell Transplant

EXPERIMENTAL

Allogeneic Stem Cell Transplant will be performed on eligible patients

Biological: Allogeneic Stem Cell Transplant; Drug: Cyclophosphamide; Drug: G-CSF; Drug: Campath-1h; Drug: Fludarabine; Drug: Tacrolimus; Drug: Mesna

Interventions

Autologous Stem Cell Transplant BIOLOGICAL

Autologous Hematopoietic Stem Cell Transplant will be performed after conditioning

Also known as: AutologousHematopoietic Stem Cell Transplantation

Autologous Stem Cell Transplant

Allogeneic Stem Cell Transplant BIOLOGICAL

Allogeneic Stem Cell Transplant will be performed after conditioning

Also known as: Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic Stem Cell Transplant; Autologous Stem Cell Transplant

Cyclophosphamide DRUG

Causes prevention of the cell division

Also known as: Cytoxan, Neosar

Allogeneic Stem Cell Transplant; Autologous Stem Cell Transplant

ATG (rabbit) DRUG

A rabbit polyclonal antibody to lymphocyte

Also known as: Thymoglobulin

Autologous Stem Cell Transplant

G-CSF DRUG

Hematopoietic growth factor

Also known as: Neupogen

Allogeneic Stem Cell Transplant; Autologous Stem Cell Transplant

Campath-1h DRUG

Humanized monoclonal antibody against CD52 antigen

Also known as: Alemtuzumab

Allogeneic Stem Cell Transplant

Fludarabine DRUG

inhibits DNA synthesis or repair

Also known as: Fludara

Allogeneic Stem Cell Transplant

Tacrolimus DRUG

immune suppressive drug

Also known as: FK506, PROGRAF

Allogeneic Stem Cell Transplant

Mesna DRUG

Mesna is a drug used to protect the bladder from the effects of the chemotherapy drugs

Also known as: Mesnex

Allogeneic Stem Cell Transplant; Autologous Stem Cell Transplant

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Age 16 to 60 years old at the time of pretransplant evaluation.
• \. An established diagnosis of systemic necrotizing vasculitis (Wegener's granulomatous, polyarteritis nodosum (PAN), allergic angiitis granulomatous (AAG, also known as Churg Strauss syndrome), microscopic polyangiitis (MPA), or overlap syndrome)Temporal arteritis, or mixed cryoglobulinemia or primary central nervous system vasculitis AND failure of corticosteroids and any of the following at least 6 months of oral or IV cytoxan, rituximab, or cellcept. (Failure defined as: a) patients with a high disease activity and involvement of internal organs as measured by increased FFS \> 2 and/or BVAS \> 20, or b) patients who develop recurrent flares with subsequent progressive organ damage.)
• Neurovascular Behcets with recurrent oral and/or genital lesions confirmed by culture to be herpes negative, MRI findings consistent with CNS vasculitis, recurrent neurological symptoms, and clinical confirmation by a Neurologist (e.g., Dr. Rama Gourimeni) AND failure of at least 3 months of oral or IV cytoxan.
• Pulmonary or neurovascular Sjogrens with positive SSA/SSB confirmed by a rheumatologist and neurologist (if CNS involved) or pulmonologist (if lungs involved) and either recurrent neurologic attacks or progressive pulmonary compromise (dyspnea on exertion, decreased DLCO or CT findings of active disease) despite at least 6 months of intravenous monthly pulse cyclophosphamide.
• \. Patient eligibility must be confirmed by two Rheumatologists. For patients with neurovascular Behcets, eligibility need only be confirmed by a neurologist.
• \. A minimum CD34+ cell dose of 2.0 x 10e6/kg post-selection.

You may not qualify if:

• \. Significant end organ damage such as:
• LVEF \<40% or deterioration of LVEF during exercise test on MUGA or echocardiogram unless due to active disease.
• Untreated life-threatening arrhythmia.
• Active ischemic heart disease or heart failure.
• DLCO \< 40% of predicted value unless due to active disease.
• Serum creatinine \> 2.5 mg/dl, unless due to active disease.
• 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.
• \. Active infection, excluding asymptomatic bacteruria or vaginal candidiasis.
• \. Active hepatitis B (HBSAg positive) or active hepatitis C (PCR positive blood lymphocytes).

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Vasculitis

Interventions

Cyclophosphamide; thymoglobulin; Granulocyte Colony-Stimulating Factor; Filgrastim; Alemtuzumab; fludarabine; fludarabine phosphate; Tacrolimus; Mesna

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 15, 2006
• First Posted: January 18, 2006
• Study Start: August 1, 2003
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 2, 2018
• Results First Posted: August 2, 2018

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)