Rheumatoid ArthritisPhase 1NCT00282412
Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism
A Phase 1 study testing Hematopoietic Stem Cell Transplantation, Fludarabine and Cyclophosphamide in people with Rheumatoid Arthritis, run by Northwestern University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Hematopoietic Stem Cell Transplantation, Fludarabine and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to Jun 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
Official title: Rheumatoid Arthritis: Tolerance Induction by Mixed Chimerism
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Hematopoietic Stem Cell Transplantation, Fludarabine, Cyclophosphamide, Campath 1H, GCSF
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Stem Cell TransplantationBiological
Allogeneic Hematopoietic Stem Cell Transplantation
FludarabineDrug
Also called Fludara
inhibits DNA synthesis or repair
CyclophosphamideDrug
Also called Cytoxan, Neosar
Causes prevention of cell division by forming adducts with DNA
Campath 1HDrug
Also called Alemtuzumab
humanized monoclonal antibody against CD52 antigen
GCSFDrug
Also called Neupogen
Hematopoietic growth factor
CyclosporinsDrug
Also called CSA
immune suppressive drug
Also called Cellcept
immune suppressive drug
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Allogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA Receives: Biological: Hematopoietic Stem Cell Transplantation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Campath 1H; Drug: GCSF; Drug: Cyclosporins; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
The number of participants who survived treatment
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2006 (estimated)
- Study startSep 2002
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: No participant enrolled for three years. No plan to continue study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00282412
- Sponsor's protocol ID
- DIAD RA ALLO
- Status last verified
- Jun 2017
- First submitted
- 24 Jan 2006
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rheumatoid Arthritis: Tolerance Induction by Mixed Chimerism
- ClinicalTrials.gov ID
- NCT00282412
- Acronym / sponsor ID
- DIAD RA ALLO
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No participant enrolled for three years. No plan to continue study.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Sep 2002
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 26 Jan 2006 (estimated)
- Results
- Posted 30 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Biological: Hematopoietic Stem Cell Transplantation, Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Campath 1H, Drug: GCSF, Drug: Cyclosporins, Drug: Mycophenolate MofetilAllogeneic Hematopoietic Stem Cell Transplantation will be performed on eligible patients diagnosed with RA |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hematopoietic Stem Cell TransplantationAllogeneic Hematopoietic Stem Cell Transplantation | Biological | Hematopoietic Stem Cell Transplantation |
| FludarabineAlso: Fludarainhibits DNA synthesis or repair | Drug | Hematopoietic Stem Cell Transplantation |
| CyclophosphamideAlso: Cytoxan, NeosarCauses prevention of cell division by forming adducts with DNA | Drug | Hematopoietic Stem Cell Transplantation |
| Campath 1HAlso: Alemtuzumabhumanized monoclonal antibody against CD52 antigen | Drug | Hematopoietic Stem Cell Transplantation |
| GCSFAlso: NeupogenHematopoietic growth factor | Drug | Hematopoietic Stem Cell Transplantation |
| CyclosporinsAlso: CSAimmune suppressive drug | Drug | Hematopoietic Stem Cell Transplantation |
| Mycophenolate MofetilAlso: Cellceptimmune suppressive drug | Drug | Hematopoietic Stem Cell Transplantation |
Primary outcome
Survival
Time frame: up to 5 years
The number of participants who survived treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Burt, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hematopoietic Stem Cell Transplantation, Fludarabine and Cyclophosphamide in people with Rheumatoid Arthritis, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2018.