Hematopoietic Stem Cell Support in Patients With Refractory Sarcoidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00282438
First received: January 24, 2006
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Sarcoidosis is a disease believed to be due to immune cells, cells which normally protect the body, but are now attacking lungs, heart, nerves, or other organs or systems within the body. As a result, the affected organs or systems fail to work properly causing difficulty breathing; heart failure; inability of the nerves to respond properly causing numbing, tingling, pain, and progressive muscle weakness; or other symptoms depending on the organ or body system involved. 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 the previously collected blood stem cells will stop the progression of sarcoidosis. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the high dose cyclophosphamide and ATG is to destroy the cells in the immune system. The purpose of the stem cell infusion is to evaluate whether this treatment will produce a normal immune system that will no longer attack the body.


Condition Intervention Phase
Sarcoidosis
Biological: Hematopoietic stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplant in Patients With Refractory Sarcoidosis: A Phase I/II Trial

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Toxicity;Survival;Time to disease progression [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: December 2003
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation will be performed after conditioning
Biological: Hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > or = 18years and < or = 60 years at the time of pretransplant evaluation.
  2. Definitive diagnosis of sarcoidosis in pathologic specimen.
  3. Patients who failed to respond to conventional treatment of at least 3 months duration with corticosteroids (equivalent dosage of prednisone 1.0mg/kg/day to start). Patients must also have failed two or more of the followings: TNF inhibitors (etanercept, infliximab), methotrexate, azathioprine, 6-MP, cyclosporin, tacrolimus, mycophenolate mofetil, gold, dapsone, colchicine, chloroquine/hydroxychloroquine or any other immunosuppressive or modulating drugs.
  4. Failure of therapy defined by (not caused by unrelated conditions) any one of following:

    • Progressive pulmonary disease (stage II or III) defined by decline in pulmonary function (DLCo, VC or FEV1) of 15% or more over 12 months.
    • Progressive CNS disease (worsening symptoms such as paraparesis or medically refractory seizure).
    • Persistent peripheral neuropathy (one of following):

      1. Persistent muscle weakness Grade 3/5 or worse (MRC) in at least one movement (e.g. ankle dorsiflexion) in two limbs.
      2. Persistent cranial nerve involvement such as persistent facial diplegia.
      3. Persistent incapacitating sensory loss (e.g. gait ataxia, falls > 1/month).
    • Progressive loss of vision.
    • Persistent hypercalcemia.
  5. Cardiac sarcoidosis that is proven by cardiac biopsy (patients with proven cardiac sarcoidosis do not need to meet the eligibility criteria listed in #'s 3 and 4 above).

Exclusion Criteria:

  1. Alternative diagnosis.
  2. Noncompliance to medical care.
  3. > 10 pack-year history of cigarette smoking if lung disease is the major problem.
  4. Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is due to the disease itself.
  5. Significant end organ damage such as:

    1. Overt congestive heart failure (NYHA Class III or IV).
    2. Active ischemic heart disease, s/p myocardial infarction within 6 months, s/p unstable angina within 3 months, s/p CVA within 6 months, s/p hospitalization for CHF within 3 months.
    3. Untreated life-threatening arrhythmia.
    4. Pulmonary hypertension > 40 mmHg.
    5. End-stage lung disease (TLC < 55%, FVC < 55%, or DLCO < 40% of predicted value).
    6. Serum creatinine > 2.5 or creatinine clearance < 30 ml/min.
    7. Liver cirrhosis, transaminases > 3x normal or bilirubin > 2.0 unless due to Gilbert's disease.
  6. HIV positive.
  7. 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.
  8. 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.
  9. 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.
  10. Significant psychological issues, social issues, psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  11. Inability to give informed consent.
  12. Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282438

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

Locations
United States, Illinois
Northwestern University, Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sub-Investigator: Mihai Gheorghiade, MD         
Sub-Investigator: Robert Sufit, MD         
Sub-Investigator: Kathleen Quigley, R.N         
Sub-Investigator: Kimberly Yaung, R.N         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00282438     History of Changes
Other Study ID Numbers: NU FDA SARC.2003
Study First Received: January 24, 2006
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoidosis
Lymphoproliferative Disorders
Lymphatic Diseases

ClinicalTrials.gov processed this record on August 20, 2014