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Immuno-ablation With Chemoimmunoradiation and Autologous Stem Cell Transplant for Churg-Strauss Syndrome

Primary Purpose

Churg-Strauss Syndrome

Status

Terminated

Phase

Early Phase 1

Locations

Study Type

Interventional

Intervention

HPC cell infusion

About this trial

This is an interventional treatment trial for Churg-Strauss Syndrome

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.

Exclusion Criteria:

Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.
Previous allergy to cyclophosphamide, rituximab, mepolizumab, azathioprine.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HPC cell infusion

Arm Description

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.

Outcomes

Primary Outcome Measures

number of patients with adverse events during treatment

toxicity will be assessed by the assessment of adverse events related to therapy

Secondary Outcome Measures

hematologic recovery

as measured by complete blood counts

graft failure rate

resolution of eosinophilia

as measured by complete blood counts

Full Information

NCT ID

NCT02728271

First Posted

March 14, 2016

Last Updated

July 28, 2017

Sponsor

Mounzer Agha

1. Study Identification

Unique Protocol Identification Number

NCT02728271

Brief Title

Immuno-ablation With Chemoimmunoradiation and Autologous Stem Cell Transplant for Churg-Strauss Syndrome

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Terminated

Why Stopped

PI left the institution

Study Start Date

April 2016 (Actual)

Primary Completion Date

July 22, 2016 (Actual)

Study Completion Date

August 20, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mounzer Agha

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Churg-Strauss Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HPC cell infusion

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

HPC cell infusion

Intervention Description

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.

Primary Outcome Measure Information:

Title

number of patients with adverse events during treatment

Description

toxicity will be assessed by the assessment of adverse events related to therapy

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.

Secondary Outcome Measure Information:

Title

hematologic recovery

Description

as measured by complete blood counts

Time Frame