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

NCT02728271 | Terminated Early Phase 1

• 1 other identifier: 15-146
• Study Type: interventional
• Target: 1
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Churg-Strauss Syndrome

Outcome Measures

Primary Outcomes (1)

• number of patients with adverse events during treatment

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

  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

  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

  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

  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.

Other Outcomes (6)

• regression of antineutrohil cytoplasmic autoantibody (ANCA) titers

  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.

• change in the total lung capacity

  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.

• change in the diffusing capacity of the lungs for carbon monoxide (DLCO)

  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.

Study Arms (1)

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.

Biological: HPC cell infusion

Interventions

HPC cell infusion BIOLOGICAL

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.

HPC cell infusion

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Mounzer Agha: lead

MeSH Terms

Conditions

Churg-Strauss Syndrome

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Mounzer Agha, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: April 5, 2016
• Study Start: April 1, 2016
• Primary Completion: July 22, 2016
• Study Completion: August 20, 2016
• Last Updated: August 1, 2017

Record last verified: 2016-03