Hematopoietic Stem Cell Support in Patients With Refractory Sarcoidosis

NCT00282438 | Terminated Phase 1 Results

• 1 other identifier: NU FDA SARC.2003
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sarcoidosis

Outcome Measures

Primary Outcomes (3)

• Presence of Toxicity

  Daily assessment will be made with regards to toxicity by one of the protocol investigators.National Cancer Institute Common Toxicity Criteria will be used to grade all non-hematologic toxicities. Toxicity grades as follows: 1 = Mild; 2 = Moderate; 3 = Severe and undesirable; 4 = life threatening or disabling ; 5 = Death

  For length of hospital stay (until discharge).

• Survival

  Patient has not died.

  Participants are to be followed at 6 months and then yearly until 5 years

• Time to Disease Progression

  Worsening symptoms, pulmonary function studies, cardiac function and arrhythmia including EKG assessments, and neurological symptoms.

  Participants are to be followed at 6 months and then yearly until 5 years

Study Arms (2)

Autologous hematopoietic stem cell transplantation

EXPERIMENTAL

Autologous stem cells will be injected after conditioning

Biological: Autologous hematopoietic stem cell transplantation

Allogeneic stem cell transplantation

EXPERIMENTAL

Allogeneic stem cells will be injected after conditioning

Biological: Allogeneic stem cell transplantation

Interventions

Autologous hematopoietic stem cell transplantation BIOLOGICAL

Autologous hematopoietic stem cells will be injected after conditioning

Also known as: Autologous stem cell injection

Autologous hematopoietic stem cell transplantation

Allogeneic stem cell transplantation BIOLOGICAL

Allogeneic stem cells will be injected after conditioning

Allogeneic stem cell transplantation

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18years and ≤ 60 years at the time of pretransplant evaluation.
• Definitive diagnosis of sarcoidosis in pathologic specimen.
• 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.
• 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):
• Persistent muscle weakness Grade 3/5 or worse (MRC) in at least one movement (e.g. ankle dorsiflexion) in two limbs.
• Persistent cranial nerve involvement such as persistent facial diplegia.
• Persistent incapacitating sensory loss (e.g. gait ataxia, falls \> 1/month).
• Progressive loss of vision.
• Persistent hypercalcemia.
• Cardiac sarcoidosis that is proven by cardiac biopsy or cardiac MRI.

You may not qualify if:

• Alternative diagnosis.
• Noncompliance to medical care.
• \> 10 pack-year history of cigarette smoking if lung disease is the major problem.
• 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:
• Overt congestive heart failure (NYHA Class III or IV).
• 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.
• Untreated life-threatening arrhythmia.
• Pulmonary hypertension \> 40 mmHg.
• End-stage lung disease (TLC \< 55%, FVC \< 55%, or DLCO \< 40% of predicted value).
• Serum creatinine \> 2.5 or creatinine clearance \< 30 ml/min.
• Liver cirrhosis, transaminases \> 3x normal or bilirubin \> 2.0 unless due to Gilbert's 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.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Sarcoidosis

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Two patients had been enrolled on trial. One underwent autologous HSCT and relapsed early after the transplant. The second participant underwent allogeneic HSCT and died 70 days after the transplant and the study has been terminated.

Results Point of Contact

• Title: Dr Richard Burt, Chief, Division of Immunotherapy, Department of Medicine
• Organization: Northwestern University

rburt@northwestern.edu

312-695-4960

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 24, 2006
• First Posted: January 26, 2006
• Study Start: December 1, 2003
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 31, 2018
• Results First Posted: February 24, 2017

Record last verified: 2018-08

Locations

US (1)