Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism

NCT00282412 | Terminated Phase 1 Results DMC

• 1 other identifier: DIAD RA ALLO
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis disease is believed to be due to immune cells, cells that normally protect the body and are now causing damage to the body. Risk of death is highest in people with twenty or more joints actively involved with disease, positive rheumatoid factor, an elevated sedimentation rate (laboratory measures of active inflammation), and patients with limitation of daily activities (trouble doing simple things like opening a carton of milk). In these high risk patients, life is significantly shortened. Death is usually from heart disease, kidney failure, neck dislocation, broken hip bones, or blood clots to the lung. In this study we use moderate dose chemotherapy (cyclophosphamide and fludarabine) and CAMPATH-1H (a protein that kills the immune cells that are thought to be causing the disease), followed by infusion of blood stem cells that have been collected from the patient's brother or sister (allogeneic stem cell transplant). The purpose of the moderate dose chemotherapy and CAMPATH-1H is to destroy the cells in the immune system and to allow the cells from the patient's brother or sister to grow. The purpose of the stem cell infusion is to restore blood cell production, which will be severely impaired by the moderate dose chemotherapy and CAMPATH-1H, and to produce a normal immune system that will no longer attack the body.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Survival

  The number of participants who survived treatment

  up to 5 years

Study Arms (1)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA

Biological: Hematopoietic Stem Cell Transplantation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Campath 1H; Drug: GCSF; Drug: Cyclosporins; Drug: Mycophenolate Mofetil

Interventions

Hematopoietic Stem Cell Transplantation BIOLOGICAL

Allogeneic Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Fludarabine DRUG

inhibits DNA synthesis or repair

Also known as: Fludara

Hematopoietic Stem Cell Transplantation

Cyclophosphamide DRUG

Causes prevention of cell division by forming adducts with DNA

Also known as: Cytoxan, Neosar

Hematopoietic Stem Cell Transplantation

Campath 1H DRUG

humanized monoclonal antibody against CD52 antigen

Also known as: Alemtuzumab

Hematopoietic Stem Cell Transplantation

GCSF DRUG

Hematopoietic growth factor

Also known as: Neupogen

Hematopoietic Stem Cell Transplantation

Cyclosporins DRUG

immune suppressive drug

Also known as: CSA

Hematopoietic Stem Cell Transplantation

Mycophenolate Mofetil DRUG

immune suppressive drug

Also known as: Cellcept

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age \> 18 and \< 60 years at time of pre-transplant evaluation.
• An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria.
• Patients must have failed an autologous hematopoietic transplant or have failed to respond to either methotrexate or leflunomide in combination with a TNF inhibitor. Failure is defined as an inability to tolerate treatment with at least 6 swollen joints and 20 involved joints or inability to answer at least 70% of HAQ questions with "no difficulty" despite 2 or more months of treatment.
• Ability to give informed consent.
• Patient must have a HLA matched sibling donor at the A, B, C, and DR loci to proceed or HLA matched cord blood donor.
• If donor is HLA matched cord blood, cord blood stem cells will be obtained from the NMDP (1-800-548-1375) and one or two units of HLA matched cord blood will be infused on day zero.

You may not qualify if:

• History of coronary artery disease, or documented congestive heart failure.
• 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 chemoradiotherapy.
• 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 head and neck cancer, or stage I breast cancer will be considered on an individual basis.
• Positive pregnancy test, inability or unwillingness 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.
• FEV1/FVC \< 70% of predicted, DLCO \< 40% of predicted.
• Resting LVEF \< 45 %.
• Bilirubin \> 2.0 mg/dl (unless due to Gilberts), transferase (AST) \> 2.5 x upper limit of normal.
• Serum creatinine \> 2.0 mg/dl.
• Age \< 18 years.
• Positive for HIV-1, HIV-2, HTLV-I, HTLV-II.
• Active hepatitis B or C.
• History of a malignancy except for a localized cancer such as skin cancer that is deemed cured.
• History of myocardial infarction or congestive heart failure.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Hematopoietic Stem Cell Transplantation; fludarabine; fludarabine phosphate; Cyclophosphamide; Alemtuzumab; Filgrastim; Cyclosporins; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

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: 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 24, 2006
• First Posted: January 26, 2006
• Study Start: September 1, 2002
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)