MYOPATHYPhase 1NCT00278564
Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
A Phase 1 study testing Hematopoietic stem cell transplantation, Cyclophosphamide and Mesna in people with MYOPATHY, run by Northwestern University at 1 site in United States.
Trial summary
Myositis is a disease, believed to be due to immune cells, cells which normally protect the body, but are now attacking the muscles and other organ systems within body. As a result, the affected muscles and organs fail to work properly causing weakness, difficulty swallowing, skin rash, respiratory problems, heart… Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- MYOPATHY
- What is being tested?
- Hematopoietic stem cell transplantation, Cyclophosphamide and Mesna
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Jul 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.
- An established diagnosis of polymyositis, dermatomyositis, juvenile polymyositis/dermatomyositis, and myositis associated with other collagen diseases. Diagnosis requires electrophysiological studies and histopathologic features. MRI evidence of muscle inflammation or histological evidence of active myositis is mandatory at entry. If patient had dermatomyositis/polymyositis associated with malignancy, the patient has to be free of malignancy for 5 years and considered to be cured.
- Patients who failed conventional treatment of at least 3 months duration including high-dose corticosteroids (equivalent dosage of prednisone >1.0 mg/kg/day to start), and must also have failed two or more of the followings: cyclophosphamide, azathioprine, 6-MP, methotrexate, tacrolimus, cyclosporin A, mycophenolate mofetil, TNF inhibitor (e.g. etanercept), IVIG or any other immunosuppressive drugs or immune modulating drugs.
- Failure is defined by (one or more of the following) (not caused by unrelated conditions):
- Persistent muscle weakness (grade 4/5 or worse by MRC) with elevation of muscle derived enzymes (CPK, aldolase)
- Worsening pulmonary function especially %VC or DLCo > 15% over 12 months indicating active alveolitis.
- Abnormal EKG or echocardiographic evidence of cardiomyopathy.
- Presence of progressive joint contracture, progressive calcinosis, vasculitis, or skin ulcers in juvenile dermatomyositis/polymyositis.
Who cannot join
- Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is due to the disease itself.
- Significant end organ damage such as (not caused by IIM):
- LVEF <40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
- Untreated life-threatening arrhythmia.
- Active ischemic heart disease or heart failure.
- DLCo <40% or FEV1/FEV < 50%.
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- Serum creatinine >2.5 or creatinine clearance <30ml/min.
- Liver cirrhosis, transaminases >3x of normal limits or bilirubin >2.0 unless due to Gilbert disease.
- 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 treatment.
- 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 (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
- Positive pregnancy test, inability or unable 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.
- Inability to give informed consent.
- Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul.
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: High Dose Cyclophosphamide & ATG With Hematopoietic Stem Cell Transplantation in Patients With Refractory Idiopathic Inflammatory Myopathy Diseases: A Phase I Trial
Myositis is a disease, believed to be due to immune cells, cells which normally protect the body, but are now attacking the muscles and other organ systems within body. As a result, the affected muscles and organs fail to work properly causing weakness, difficulty swallowing, skin rash, respiratory problems, heart problems, joint stiffness, soft tissue calcification and vasculitis (blood circulation problems). The likelihood of progression of this disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide (a drug which reduces the function of the immune system) and ATG (a protein that kills the immune cells that are thought to be causing this disease), followed by return of previously collected blood stem cells will stop the progression of myositis.
Read the detailed description
Conditioning Regimen (In order to assure sterility testing, a minimum of 14 days will be required between stem cell collection and starting the conditioning regimen).
The conditioning regimen is outlined in below:
Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day -5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% (actual weight minus ideal weight).
Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting at 10AM each dose. Weight base is calculated same as cyclophosphamide as above.
1ATG (rabbit) 0.5 mg/kg on day -6 and 1mg/kg on day -5, -4, -3, -2 and -1 (total 5.5mg/kg, no dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least 1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and diphenhydramine 25 mg po/IV 30 minutes before the infusion.
Methylprednisolone- A suggested dose of 250mg IV should be administered 30 minutes before each ATG infusion.
Hydration- A suggested rate of 125 cc/hr NS should be given starting 6 hours before the first cyclophosphamide dose and continued until 24 hours after the last cyclophosphamide dose. The rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. Minimum target urine output is 2 liters/m2/day
G-CSF 5 mcg/kg/day will be given subcutaneously and continued until the absolute neutrophil counts reaches at least 500/µl.
Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after stem cell infusion.
- Conditions
- MYOPATHY
- Being tested
- Hematopoietic stem cell transplantation, Cyclophosphamide, Mesna, ATG(rabbit), Methylprednisolone
- Medical subject headings
- Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic stem cell transplantationBiological
Autologous hematopoietic stem cell transplantation
CyclophosphamideDrug
Also called Cytoxan
MesnaDrug
ATG(rabbit)Drug
G-CSFDrug
RituxanDrug
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic stem cell transplantation | Experimental | Intervention as hematopoietic stem cells transplantation after conditioning regimen: Autologous hematopoietic stem cells will be injected after conditioning regimen Receives: Biological: Hematopoietic stem cell transplantation; Drug: Cyclophosphamide; Drug: Mesna; Drug: ATG(rabbit); Drug: Methylprednisolone; Drug: G-CSF; Drug: Rituxan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Survival
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 posted18 Jan 2006 (estimated)
- Study startSep 2005
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: high relapse rate
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 MYOPATHYStudies 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
- 7 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
- NCT00278564
- Sponsor's protocol ID
- NU FDA IIM.Auto2003
- Status last verified
- Jun 2017
- First submitted
- 15 Jan 2006
- Last updated
- 6 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose Cyclophosphamide & ATG With Hematopoietic Stem Cell Transplantation in Patients With Refractory Idiopathic Inflammatory Myopathy Diseases: A Phase I Trial
- ClinicalTrials.gov ID
- NCT00278564
- Acronym / sponsor ID
- NU FDA IIM.Auto2003
- Conditions
- MYOPATHY
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: high relapse rate
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 18 Jan 2006 (estimated)
- Results
- Posted 6 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Myositis is a disease, believed to be due to immune cells, cells which normally protect the body, but are now attacking the muscles and other organ systems within body. As a result, the affected muscles and organs fail to work properly causing weakness, difficulty swallowing, skin rash, respiratory problems, heart problems, joint stiffness, soft tissue calcification and vasculitis (blood circulation problems). The likelihood of progression of this disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide (a drug which reduces the function of the immune system) and ATG (a protein that kills the immune cells that are thought to be causing this disease), followed by return of previously collected blood stem cells will stop the progression of myositis.
Detailed description
Conditioning Regimen (In order to assure sterility testing, a minimum of 14 days will be required between stem cell collection and starting the conditioning regimen).
The conditioning regimen is outlined in below:
Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day -5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% (actual weight minus ideal weight).
Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting at 10AM each dose. Weight base is calculated same as cyclophosphamide as above.
1ATG (rabbit) 0.5 mg/kg on day -6 and 1mg/kg on day -5, -4, -3, -2 and -1 (total 5.5mg/kg, no dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least 1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and diphenhydramine 25 mg po/IV 30 minutes before the infusion.
Methylprednisolone- A suggested dose of 250mg IV should be administered 30 minutes before each ATG infusion.
Hydration- A suggested rate of 125 cc/hr NS should be given starting 6 hours before the first cyclophosphamide dose and continued until 24 hours after the last cyclophosphamide dose. The rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. Minimum target urine output is 2 liters/m2/day
G-CSF 5 mcg/kg/day will be given subcutaneously and continued until the absolute neutrophil counts reaches at least 500/µl.
Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after stem cell infusion.
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: Cyclophosphamide, Drug: Mesna, Drug: ATG(rabbit), Drug: Methylprednisolone, Drug: G-CSF, Drug: RituxanIntervention as hematopoietic stem cells transplantation after conditioning regimen: Autologous hematopoietic stem cells will be injected after conditioning regimen |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.
- An established diagnosis of polymyositis, dermatomyositis, juvenile polymyositis/dermatomyositis, and myositis associated with other collagen diseases. Diagnosis requires electrophysiological studies and histopathologic features. MRI evidence of muscle inflammation or histological evidence of active myositis is mandatory at entry. If patient had dermatomyositis/polymyositis associated with malignancy, the patient has to be free of malignancy for 5 years and considered to be cured.
- Patients who failed conventional treatment of at least 3 months duration including high-dose corticosteroids (equivalent dosage of prednisone >1.0 mg/kg/day to start), and must also have failed two or more of the followings: cyclophosphamide, azathioprine, 6-MP, methotrexate, tacrolimus, cyclosporin A, mycophenolate mofetil, TNF inhibitor (e.g. etanercept), IVIG or any other immunosuppressive drugs or immune modulating drugs.
- Failure is defined by (one or more of the following) (not caused by unrelated conditions):
Key exclusion criteria (15 listed)
- Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is due to the disease itself.
- Significant end organ damage such as (not caused by IIM):
- 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 treatment.
- 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 (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
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 transplantationAutologous hematopoietic stem cell transplantation | Biological | Hematopoietic stem cell transplantation |
| CyclophosphamideAlso: Cytoxan | Drug | Hematopoietic stem cell transplantation |
| Mesna | Drug | Hematopoietic stem cell transplantation |
| ATG(rabbit) | Drug | Hematopoietic stem cell transplantation |
| Methylprednisolone | Drug | Hematopoietic stem cell transplantation |
| G-CSF | Drug | Hematopoietic stem cell transplantation |
| Rituxan | Drug | Hematopoietic stem cell transplantation |
Primary outcome
Survival
Time frame: up to 5 years
Survival
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 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, Cyclophosphamide and Mesna in people with MYOPATHY, 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?
The sponsor lists 8 inclusion and 15 exclusion criteria. 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 6 Aug 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 6 Aug 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 6 Aug 2018.