Churg-Strauss SyndromeEarly Phase 1NCT02728271
Immuno-ablation With Chemoimmunoradiation and Autologous Stem Cell Transplant for Churg-Strauss Syndrome
A Early Phase 1 study testing HPC cell infusion in people with Churg-Strauss Syndrome, run by Mounzer Agha.
Trial summary
Churg-Strauss syndrome is a rare autoimmune inflammatory disease affecting medium- and small-sized blood vessels, causing asthma, abnormalities of the blood, lung diseases, and neuropathy. The main cause of death in these patients is heart attack. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Churg-Strauss Syndrome
- What is being tested?
- HPC cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- Apr 2016to 20 Aug 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
Who may be able to join
- Age 18-60, inclusive
- Subjects carry a diagnosis of Churg-Strauss syndrome, with typical clinical, pathologic, and/or radiological appearances.
- Must have a pulmonologist/immunologist providing the primary care for the Churg-Strauss syndrome and be willing to be evaluated for the Churg-Strauss syndrome who is the co-investigator in the protocol.
- Must be documented to be HIV negative.
- Subjects must be able to give written consent.
- Subjects with abscesses are eligible to enroll once the abscesses or any other significant infection has resolved.
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- Subjects must not be pregnant and will undergo a pregnancy test prior to starting the study treatment. The subjects should also be willing to take the appropriate contraception starting at least three months prior to the transplant.
- All eligible subjects will need the approval of the insurance company for the coverage of the study treatment.
- Life expectancy of more than 6 months. ECOG performance status of 0 or 1.
- No evidence of myelodysplastic on peripheral blood smear
- Baseline serum creatinine must be <1.5 mg/dL, left ventricular ejection fraction >55%, adequate pulmonary functions (oxygen saturation at room air of >90%), and AST and ALT not > 2x upper limits of normal, and no history of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma in situ of the cervix.
- Evidence for life threatening disease, including FEV1 <50% predicted (on therapy) and/or cardiac involvement (arrhythmias, failure)
- Failure to stabilize in response to prednisone (or equivalent) at doses of <20 mg per day
- Failure of at least 3 other immunosuppressives to stabilize disease, including drugs like cyclophosphamide, rituximab, mepolizumab, azathioprine.
Who cannot join
- Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.
- Previous allergy to cyclophosphamide, rituximab, mepolizumab, azathioprine.
About this study
Official title: A Pilot Study of Immuno-ablation With Chemoimmunoradiation Followed by Autologous Hematopoietic Progenitor Cell (HPC) Transplant for Adult Subjects With Churg-Strauss Syndrome
Churg-Strauss syndrome is a rare autoimmune inflammatory disease affecting medium- and small-sized blood vessels, causing asthma, abnormalities of the blood, lung diseases, and neuropathy. The main cause of death in these patients is heart attack. Without therapy, the 5-year survival in patients with Churg-Strauss syndrome is 25%. Although with the 5-year survival is increased to 62% with the appropriate therapy, many patients remain refractory to therapy. The long term outcome of these patients remains grim.
The aim of this research study is to determine if suppressing the immune system using a combination of high dose chemotherapy, antibodies, and radiation followed by stem cell transplant will abolish the 'bad' immune system and let the patient's body establish a new immune system that does not attack the blood vessels.
Read the detailed description
Churg-Strauss syndrome is a rare autoimmune inflammatory disease affecting medium- and small-sized arteries and veins and is closely related to Wegener's granulomatosis. It is also one of the diseases that are associated with antibodies to neutrophils cytoplasmic antigens (ANCAs). Patients with Churg-Strauss syndrome often present with refractory asthma, eosinophilia, pulmonary infiltrates and mononeuritis multiplex.
Corticosteroids remain the first line therapy for these patients and most patients respond to corticosteroid therapy. However, a small proportion of patients need other immunosuppressive agents such as cyclophosphamide, cyclosporine A, Rituximab, and azathioprine. Still a number of these patients remain refractory and extremely dependent on high dose corticosteroids.
The principal cause of mortality in these patients is myocarditis and myocardial infarction due to coronary arteritis. Without therapy, the 5-year survival in patients with Churg-Strauss syndrome is 25%. Although with the 5-year survival is increased to 62% with the appropriate therapy, many patients remain refractory to therapy. The long term outcome of these patients remains grim.
In this study, the investigators hypothesize that the addition of total lymphatic irradiation to the combination of high dose cyclophosphamide and antithymocyte globulins can be given safely to these patients and will not only induce disease remission in patients with refractory Churg-Strauss syndrome, it would also induce sustained and long period of medication-free remission in these patients. Since this combination preparative regimen has never been used previously, the investigators will test this hypothesis in a pilot study.
- Conditions
- Churg-Strauss Syndrome
- Being tested
- HPC cell infusion
- Medical subject headings
- Churg-Strauss Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HPC cell infusionBiological
Administration of total lymphatic irradiation, antithymocyte globulins, and high dose cyclophosphamide, followed by the infusion of autologous stem cells.
Patients will not receive any cyclosporin A, rituximab, or azathioprine post transplant.
| Study group | Role | What they receive |
|---|---|---|
| HPC cell infusion | Experimental | Autologous HPC will be infused within 24 hours of completing the chemotherapy. A total of 5 x 106/kg CD34+ HPC will be infused. The remaining HPC will be stored as back-up, to be used in case of graft failure. Receives: Biological: HPC cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients with adverse events during treatment
toxicity will be assessed by the assessment of adverse events related to therapy
Measured: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or if the patient dies, whichever occurs first.
Secondary outcomes (3)
hematologic recovery
as measured by complete blood counts
Measured: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
graft failure rate
Measured: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
resolution of eosinophilia
as measured by complete blood counts
Measured: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2016 (estimated)
- Study startApr 2016
- Primary completion22 Jul 2016
- Study completion20 Aug 2016
Why it stopped: PI left the institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Churg-Strauss SyndromeStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mounzer Agha
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mounzer Agha, University of Pittsburgh
- Investigators
- Mounzer Agha, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02728271
- Sponsor's protocol ID
- 15-146
- Status last verified
- Mar 2016
- First submitted
- 14 Mar 2016
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Immuno-ablation With Chemoimmunoradiation Followed by Autologous Hematopoietic Progenitor Cell (HPC) Transplant for Adult Subjects With Churg-Strauss Syndrome
- ClinicalTrials.gov ID
- NCT02728271
- Acronym / sponsor ID
- 15-146
- Conditions
- Churg-Strauss Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left the institution
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Mounzer AghaUniversity, hospital or other
- Study start
- Apr 2016 (actual)
- Primary completion
- 22 Jul 2016 (actual)
- Study completion
- 20 Aug 2016 (actual)
- First posted
- 5 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Churg-Strauss syndrome is a rare autoimmune inflammatory disease affecting medium- and small-sized blood vessels, causing asthma, abnormalities of the blood, lung diseases, and neuropathy. The main cause of death in these patients is heart attack. Without therapy, the 5-year survival in patients with Churg-Strauss syndrome is 25%. Although with the 5-year survival is increased to 62% with the appropriate therapy, many patients remain refractory to therapy. The long term outcome of these patients remains grim.
The aim of this research study is to determine if suppressing the immune system using a combination of high dose chemotherapy, antibodies, and radiation followed by stem cell transplant will abolish the 'bad' immune system and let the patient's body establish a new immune system that does not attack the blood vessels.
Detailed description
Churg-Strauss syndrome is a rare autoimmune inflammatory disease affecting medium- and small-sized arteries and veins and is closely related to Wegener's granulomatosis. It is also one of the diseases that are associated with antibodies to neutrophils cytoplasmic antigens (ANCAs). Patients with Churg-Strauss syndrome often present with refractory asthma, eosinophilia, pulmonary infiltrates and mononeuritis multiplex.
Corticosteroids remain the first line therapy for these patients and most patients respond to corticosteroid therapy. However, a small proportion of patients need other immunosuppressive agents such as cyclophosphamide, cyclosporine A, Rituximab, and azathioprine. Still a number of these patients remain refractory and extremely dependent on high dose corticosteroids.
The principal cause of mortality in these patients is myocarditis and myocardial infarction due to coronary arteritis. Without therapy, the 5-year survival in patients with Churg-Strauss syndrome is 25%. Although with the 5-year survival is increased to 62% with the appropriate therapy, many patients remain refractory to therapy. The long term outcome of these patients remains grim.
In this study, the investigators hypothesize that the addition of total lymphatic irradiation to the combination of high dose cyclophosphamide and antithymocyte globulins can be given safely to these patients and will not only induce disease remission in patients with refractory Churg-Strauss syndrome, it would also induce sustained and long period of medication-free remission in these patients. Since this combination preparative regimen has never been used previously, the investigators will test this hypothesis in a pilot study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HPC cell infusion | Experimental | Biological: HPC cell infusionAutologous HPC will be infused within 24 hours of completing the chemotherapy. A total of 5 x 106/kg CD34+ HPC will be infused. The remaining HPC will be stored as back-up, to be used in case of graft failure. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Age 18-60, inclusive
- Subjects carry a diagnosis of Churg-Strauss syndrome, with typical clinical, pathologic, and/or radiological appearances.
- Must have a pulmonologist/immunologist providing the primary care for the Churg-Strauss syndrome and be willing to be evaluated for the Churg-Strauss syndrome who is the co-investigator in the protocol.
- Must be documented to be HIV negative.
- Subjects must be able to give written consent.
Key exclusion criteria (2 listed)
- Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.
- Previous allergy to cyclophosphamide, rituximab, mepolizumab, azathioprine.
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 |
|---|---|---|
| HPC cell infusionAdministration of total lymphatic irradiation, antithymocyte globulins, and high dose cyclophosphamide, followed by the infusion of autologous stem cells. Patients will not receive any cyclosporin A, rituximab, or azathioprine post transplant. | Biological | HPC cell infusion |
Primary outcome
number of patients with adverse events during treatment
Time frame: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or if the patient dies, whichever occurs first.
toxicity will be assessed by the assessment of adverse events related to therapy
3 secondary outcomes
hematologic recovery
Time frame: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
graft failure rate
Time frame: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
resolution of eosinophilia
Time frame: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or until the patient dies, whichever occurs first.
Results and safety
The study was stopped early (reason given: PI left the institution). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
Related trials for Churg-Strauss Syndrome
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Longitudinal Study for Eosinophilic Granulomatosis With Polyangiitis
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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.
Mounzer Agha, MD principal investigator
University of Pittsburgh
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing HPC cell infusion in people with Churg-Strauss Syndrome, run by Mounzer Agha.
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 14 inclusion and 2 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 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: PI left the institution). Results are not available in the source record.
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?
number of patients with adverse events during treatment (time frame: change from baseline at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 months and then every 12 months, up to 100 months or if the patient dies, whichever occurs first.). 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 1 Aug 2017.