search
Back to results

Stem Cell Support in Patients With Rheumatoid Arthritis

Primary Purpose

RHEUMATOID ARTHRITIS

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Immune ablation and hematopoietic stem cell transplant
Sponsored by
Richard Burt, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for RHEUMATOID ARTHRITIS

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Physiologic age < 60 years old or >18 years old. An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria, and a positive rheumatoid factor will be required. Patients must have failed two disease-modifying agents, such as methotrexate, plaquenil, gold, azathioprine, asulfidine or D-penicillamine. Patients must have six (6) swollen joints from active RA and either thirty (30) or greater involved joints (swelling, tenderness, deformity, pain on motion, or decreased motion), or have answered less than 75 percent of Health Assessment Questionnaire (HAQ) questions "without any difficulty." A harvest of PBSC greater than 1.4 x 106 CD34+ cells /kg after CD34+ selection will be necessary for the patient to proceed to transplant. Ability to give informed consent Patients with Juvenile Rheumatoid Arthritis (JRA) will be candidates if disease onset is polyarthritic or systemic and they have at least 6 swollen joints and have failed corticosteroids and two disease-modifying drugs Exclusion Criteria: HIV positive History of coronary artery disease, or congestive heart failure. 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 < 75% of predicted, DLCO < 50% of predicted. Resting LVEF < 45 % Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal Serum creatinine > 2.0 mg/dl Platelet count less than 100,000/ul, ANC less than 1000/ul History of allergy to eggs or murine proteins Known hypersensitivity to E. coli derived proteins

Sites / Locations

  • Northwestern University, Feinberg School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

heatopoietic stem cell transplant

Arm Description

Outcomes

Primary Outcome Measures

Tender joint count; Swollen joint count; Patient's assessment of pain;Patient's global assessment of disease; Physician global assessment;Acute phase reactant value (erythrocyte sedimentation rate).

Secondary Outcome Measures

Full Information

First Posted
January 15, 2006
Last Updated
April 4, 2013
Sponsor
Richard Burt, MD
search

1. Study Identification

Unique Protocol Identification Number
NCT00278551
Brief Title
Stem Cell Support in Patients With Rheumatoid Arthritis
Official Title
Immune Ablation and Hematopoietic Stem Cell Support in Patients With Rheumatoid Arthritis and High Risk Factors
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Study Start Date
June 1997 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Richard Burt, MD

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Rheumatoid arthritis (RA) is a chronic illness, immunologically mediated, probably induced by the exposure to an antigen or antigens, to which immunologic tolerance is lost. The disease has a variable course, from a mild, intermittently symptomatic illness requiring only symptomatic therapy to a fulminant illness requiring dangerous immunosuppressive therapy, surgery or both. The molecular defect causing RA has not been characterized, but may involve aberrant T cell, B cell, and macrophage function. Although RA often responds to immunosuppressive medication including corticosteroids, methotrexate, azathioprine and cyclophosphamide, or to non-steroidal anti-inflammatory drugs, no therapy has been curative. In patients with severe RA, who have been unresponsive to corticosteroids, and who have more than 20 active joints or vasculitis, we propose, as a phase I-II study, complete immune ablation and subsequent reconstitution with autologous in vitro T lymphocyte depleted PBSCs harvested from the patient prior to immune ablation. The combination of high dose cyclophosphamide and anti-thymocyte globulin conditioning will be followed by rescue with autologous lymphocyte depleted PBSCs. Subsequent disease activity will be followed by: (1) RA disease activity index, (2) type and amount of therapy for RA, and (3) flow cytometry of peripheral blood lymphocyte subsets, (4) joint count, (5) patients' assessment of pain, (6) arthritis impact measurement scales (AIMS) questionnaire, (7) acute phase reactants. This study will dose standard therapy, i.e. immune suppression, to the point of complete immune ablation and subsequent recapitulation of lymphocyte ontogeny by PBSC rescue. We anticipate that this study will also form the basis to clarify further the role of the immune system in RA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RHEUMATOID ARTHRITIS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
heatopoietic stem cell transplant
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Immune ablation and hematopoietic stem cell transplant
Intervention Description
Autologous Hematopoietic Stem Cell Transplant
Primary Outcome Measure Information:
Title
Tender joint count; Swollen joint count; Patient's assessment of pain;Patient's global assessment of disease; Physician global assessment;Acute phase reactant value (erythrocyte sedimentation rate).
Time Frame
5 years after transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Physiologic age < 60 years old or >18 years old. An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria, and a positive rheumatoid factor will be required. Patients must have failed two disease-modifying agents, such as methotrexate, plaquenil, gold, azathioprine, asulfidine or D-penicillamine. Patients must have six (6) swollen joints from active RA and either thirty (30) or greater involved joints (swelling, tenderness, deformity, pain on motion, or decreased motion), or have answered less than 75 percent of Health Assessment Questionnaire (HAQ) questions "without any difficulty." A harvest of PBSC greater than 1.4 x 106 CD34+ cells /kg after CD34+ selection will be necessary for the patient to proceed to transplant. Ability to give informed consent Patients with Juvenile Rheumatoid Arthritis (JRA) will be candidates if disease onset is polyarthritic or systemic and they have at least 6 swollen joints and have failed corticosteroids and two disease-modifying drugs Exclusion Criteria: HIV positive History of coronary artery disease, or congestive heart failure. 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 < 75% of predicted, DLCO < 50% of predicted. Resting LVEF < 45 % Bilirubin > 2.0 mg/dl, transferase (AST) > 2x upper limit of normal Serum creatinine > 2.0 mg/dl Platelet count less than 100,000/ul, ANC less than 1000/ul History of allergy to eggs or murine proteins Known hypersensitivity to E. coli derived proteins
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Burt, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University, Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Stem Cell Support in Patients With Rheumatoid Arthritis

We'll reach out to this number within 24 hrs