Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism
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ClinicalTrials.gov Identifier: NCT00282412 |
Recruitment Status :
Terminated
(No participant enrolled for three years. No plan to continue study.)
First Posted : January 26, 2006
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
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Condition or disease | Intervention/treatment | Phase |
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Rheumatoid Arthritis | Biological: Hematopoietic Stem Cell Transplantation Drug: Fludarabine Drug: Cyclophosphamide Drug: Campath 1H Drug: GCSF Drug: Cyclosporins Drug: Mycophenolate Mofetil | Phase 1 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 4 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Rheumatoid Arthritis: Tolerance Induction by Mixed Chimerism |
Study Start Date : | September 2002 |
Actual Primary Completion Date : | June 2016 |
Actual Study Completion Date : | June 2016 |

Arm | Intervention/treatment |
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Experimental: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA
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Biological: Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation Drug: Fludarabine inhibits DNA synthesis or repair
Other Name: Fludara Drug: Cyclophosphamide Causes prevention of cell division by forming adducts with DNA
Other Name: Cytoxan, Neosar Drug: Campath 1H humanized monoclonal antibody against CD52 antigen
Other Name: Alemtuzumab Drug: GCSF Hematopoietic growth factor
Other Name: Neupogen Drug: Cyclosporins immune suppressive drug
Other Name: CSA Drug: Mycophenolate Mofetil immune suppressive drug
Other Name: Cellcept |
- Survival [ Time Frame: up to 5 years ]The number of participants who survived treatment

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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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 Exclusion Criteria
- 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.
- Inability to give informed consent.
- Current pregnancy.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00282412
United States, Illinois | |
Northwestern University, Feinberg School of Medicine | |
Chicago, Illinois, United States, 60611 |
Principal Investigator: | Richard Burt, MD | Northwestern University |
Responsible Party: | Richard Burt, MD, MD, Northwestern University |
ClinicalTrials.gov Identifier: | NCT00282412 |
Other Study ID Numbers: |
DIAD RA ALLO |
First Posted: | January 26, 2006 Key Record Dates |
Results First Posted: | July 30, 2018 |
Last Update Posted: | July 30, 2018 |
Last Verified: | June 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Cyclosporine Mycophenolic Acid Cyclophosphamide Fludarabine Alemtuzumab Cyclosporins Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Enzyme Inhibitors Antifungal Agents Anti-Infective Agents Dermatologic Agents Calcineurin Inhibitors Antibiotics, Antineoplastic Antibiotics, Antitubercular |