Rheumatoid Arthritis
Conditions
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.
Detailed description
Peripheral blood stem cell mobilization (PBSC) PBSC will be mobilized with G-CSF (dose may be adjusted down to 5-10 ug/kg/day by PI for toxicity, e.g. flu-like symptoms) with stem cell collection beginning on day 4 or 5. Leukapheresis may be repeated up to four consecutive days. Conditioning Regimen Immune Ablation: Fludarabine 25 mg/m2/d x 5 days (dosage should be based on adjusted body weight) will be given IV over 30 minutes in 100 cc of normal saline. Cyclophosphamide 50 mg/kg/d x 4 days (dosage should be based on adjusted body weight) will be given IV over 1 hour in 500 cc of normal saline. CAMPATH-1H 30 mg/day x 3 days (no dose adjustment) will be given IV over 2 hours in 100 cc of normal saline. Premedication with acetaminophen 650mg & benadryl 25-50mg PO/IV will be given 30-60min before infusion. These medications can be repeated as needed. Hydration approximately 200 cc /hour beginning 6 hours before cyclophosphamide and continued until 24 hours after the last cyclophosphamide dose. G-CSF will be continued until absolute neutrophil count reaches 1,000 cells/ml for three days. Cyclosporine will be started at 200 mg po BID and adjusted by HPLC levels to between 150-250 or by toxicity (e.g. tremor, renal insufficiency, TTP, etc.). CSA will be continued for 6 months unless stopped for toxicity Mycophenolate Mofetil (Cellcept) will be given 1 gram po BID and may be adjusted by toxicity (e.g. cytopenia). Cellcept will be continued for 6 months unless stopped for toxicity.
Interventions
BIOLOGICALHematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation
DRUGFludarabine
inhibits DNA synthesis or repair
DRUGCyclophosphamide
Causes prevention of cell division by forming adducts with DNA
DRUGCampath 1H
humanized monoclonal antibody against CD52 antigen
DRUGGCSF
Hematopoietic growth factor
DRUGCyclosporins
immune suppressive drug
DRUGMycophenolate Mofetil
immune suppressive drug
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria: * 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. Participant
Exclusion criteria
* 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. Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | up to 5 years | The number of participants who survived treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hematopoietic Stem Cell Transplantation Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA
Hematopoietic Stem Cell Transplantation: Allogeneic Hematopoietic Stem Cell Transplantation | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Hematopoietic Stem Cell Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 40.00 years STANDARD_DEVIATION 12.91 |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 4 |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Survival
The number of participants who survived treatment
Time frame: up to 5 years
Population: The number of participants who survived treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Survival | 2 Participants |