Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases

November 3, 2017 updated by: Richard Burt, MD, Northwestern University

High Dose Cyclophosphamide & ATG With Hematopoietic Stem Cell Transplantation in Patients With Refractory Idiopathic Inflammatory Myopathy Diseases: A Phase I Trial

Myositis is a disease, believed to be due to immune cells, cells which normally protect the body, but are now attacking the muscles and other organ systems within body. As a result, the affected muscles and organs fail to work properly causing weakness, difficulty swallowing, skin rash, respiratory problems, heart problems, joint stiffness, soft tissue calcification and vasculitis (blood circulation problems). 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 previously collected blood stem cells will stop the progression of myositis.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Conditioning Regimen (In order to assure sterility testing, a minimum of 14 days will be required between stem cell collection and starting the conditioning regimen).

The conditioning regimen is outlined in below:

Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day -5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% (actual weight minus ideal weight).

Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting at 10AM each dose. Weight base is calculated same as cyclophosphamide as above.

1ATG (rabbit) 0.5 mg/kg on day -6 and 1mg/kg on day -5, -4, -3, -2 and -1 (total 5.5mg/kg, no dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least 1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and diphenhydramine 25 mg po/IV 30 minutes before the infusion.

Methylprednisolone- A suggested dose of 250mg IV should be administered 30 minutes before each ATG infusion.

Hydration- A suggested rate of 125 cc/hr NS should be given starting 6 hours before the first cyclophosphamide dose and continued until 24 hours after the last cyclophosphamide dose. The rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. Minimum target urine output is 2 liters/m2/day

G-CSF 5 mcg/kg/day will be given subcutaneously and continued until the absolute neutrophil counts reaches at least 500/µl.

Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after stem cell infusion.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University, Feinberg School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.
  2. An established diagnosis of polymyositis, dermatomyositis, juvenile polymyositis/dermatomyositis, and myositis associated with other collagen diseases. Diagnosis requires electrophysiological studies and histopathologic features. MRI evidence of muscle inflammation or histological evidence of active myositis is mandatory at entry. If patient had dermatomyositis/polymyositis associated with malignancy, the patient has to be free of malignancy for 5 years and considered to be cured.
  3. Patients who failed conventional treatment of at least 3 months duration including high-dose corticosteroids (equivalent dosage of prednisone >1.0 mg/kg/day to start), and must also have failed two or more of the followings: cyclophosphamide, azathioprine, 6-MP, methotrexate, tacrolimus, cyclosporin A, mycophenolate mofetil, TNF inhibitor (e.g. etanercept), IVIG or any other immunosuppressive drugs or immune modulating drugs.

  4. Failure is defined by (one or more of the following) (not caused by unrelated conditions):

    • Persistent muscle weakness (grade 4/5 or worse by MRC) with elevation of muscle derived enzymes (CPK, aldolase)
    • Worsening pulmonary function especially %VC or DLCo > 15% over 12 months indicating active alveolitis.
    • Abnormal EKG or echocardiographic evidence of cardiomyopathy.
    • Presence of progressive joint contracture, progressive calcinosis, vasculitis, or skin ulcers in juvenile dermatomyositis/polymyositis.

Exclusion Criteria:

  1. Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is due to the disease itself.

  2. Significant end organ damage such as (not caused by IIM):

    • LVEF <40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
    • Untreated life-threatening arrhythmia.
    • Active ischemic heart disease or heart failure.
    • DLCo <40% or FEV1/FEV < 50%.
    • Serum creatinine >2.5 or creatinine clearance <30ml/min.
    • Liver cirrhosis, transaminases >3x of normal limits or bilirubin >2.0 unless due to Gilbert disease.
  3. HIV positive.
  4. 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.
  5. 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.
  6. 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.
  7. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  8. Inability to give informed consent.
  9. Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Hematopoietic stem cell transplantation
Intervention as hematopoietic stem cells transplantation after conditioning regimen: Autologous hematopoietic stem cells will be injected after conditioning regimen
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
Drug: Methylprednisolone
Drug: G-CSF
Drug: Mesna
Biological: Hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
Drug: ATG(rabbit)
Drug: Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: up to 5 years
Survival
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (ACTUAL)

July 1, 2016

Study Completion (ACTUAL)

July 1, 2016

Study Registration Dates

First Submitted

January 15, 2006

First Submitted That Met QC Criteria

January 15, 2006

First Posted (ESTIMATE)

January 18, 2006

Study Record Updates

Last Update Posted (ACTUAL)

August 6, 2018

Last Update Submitted That Met QC Criteria

November 3, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NU FDA IIM.Auto2003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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