Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST) (ASSIST)

March 17, 2017 updated by: Falk Hiepe, Charite University, Berlin, Germany

An Open-Label, Phase II Multicenter Cohort Study of Immunoablation With Cyclophosphamide and Antithymocyte-Globulin and Transplantation of Autologous Cd34-Enriched Hemapoietic Stem Cells Versus Currently Available Immunosuppressive/Immunomodulatory Therapy for Treatment of Refractory Systemic Lupus Erythematosus

While glucocorticoids and immunosuppressants ameliorate manifestations of SLE in many patients, current therapies are insufficient to control the disease in a subset of patients, and their clinical prognosis remains poor due to the development of vital organ failure, cumulative drug toxicity and to the increased risk of cardiovascular disease and malignancy. Immunoablative chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) has recently emerged as a promising experimental therapy for severely affected patients, providing them the potential to achieve treatment-free, long-term remission. The investigators postulate that immunoablative therapy eliminates or effectively reduces the level of autoreactive T and B lymphocytes and then regeneration of de novo immunity resets the autoreactive immune system into a self-tolerant, protective immune system resulting in prolonged and treatment-free remission.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

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

  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Universitatsmedizin Charité
        • Contact:
          • Falk Hiepe, Prof
          • Phone Number: +49 30 450 513026
        • Principal Investigator:
          • Falk Hiepe, Prof.
      • Düsseldorf, Germany, 40225
        • Recruiting
        • Universitätsklinik Düsseldorf
        • Contact:
          • Mathias Schneider, Prof.
          • Phone Number: +49 (0) 211-8117817
        • Principal Investigator:
          • Mathias Schneider, Prof.
      • Essen, Germany, 45239 Essen
        • Recruiting
        • Universitätsklinikum Essen
        • Contact:
          • Christoph Specker, Prof.
          • Phone Number: +49 (0)201-84081214
        • Principal Investigator:
          • Christoph Specker, Prof.
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitätsklinik Heidelberg
        • Contact:
          • Hanns-Marting Lorenz, Prof.
          • Phone Number: +49 (0) 6221-568044
        • Principal Investigator:
          • Hanns-Martin Lorenz, Prof.
      • Köln, Germany, 50937
        • Recruiting
        • Universitätsklinik Köln
        • Contact:
          • Andrea Rubbert-Roth, PD
          • Phone Number: +49 (0) 221-4783993
        • Principal Investigator:
          • Andrea Rubbert-Roth, PD
      • Mainz, Germany, 55101
        • Recruiting
        • Universitäsklinik Mainz
        • Contact:
          • Karin Kolbe, MD
        • Principal Investigator:
          • Karin Kolbe, MD
      • Tübingen, Germany, 72026
        • Recruiting
        • Universitatsklinik Tubingen
        • Contact:
          • Ina Kötter, PD
          • Phone Number: +49 (0) 7071-2984095
        • Principal Investigator:
          • Ina Kötter, PD
      • Würzburg, Germany, 97070
        • Recruiting
        • Universitätsklinik Würzburg
        • Contact:
          • Hans-Peter Tony, Prof.
          • Phone Number: +49 (0) 931-20170420
        • Principal Investigator:
          • Hans-Peter Tony, Prof.

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

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria
  2. Age between 18 and 60 years, inclusive
  3. Provision of informed consent

  4. Active disease, refractory to standard immunosuppressive therapy defined as:

    • BILAG level A and a SLEDAI-score of at least 10, despite treatment with high-dose corticosteroids and pulse intravenous CYC at doses of 500-1000mg/m2 for at least 6 months or mycophenolate mofetil (MMF) at doses of at least 2g -
    • Lupus nephritis with renal biopsy performed within one year prior to screening showing glomerulonephritis WHO class III or IV
    • Parenchymal disease of heart or lung
    • Neuropsychiatric lupus
    • Autoimmune cytopenia OR
    • recurrence of disease activity (defined as BILAG level A and a SLEDAI of at least 10) within one year after successful induction therapy with cyclophosphamide or MMF in the presence of an adequate maintenance therapy with either cyclophosphamide (at least 500mg/m2 monthly), mycophenolate mofetil (at least 2g daily), azathioprine (at least 1.5mg/kg/d), methotrexate (at least 15mg weekly), cyclosporine (at least 3mg/kg/d) in patients with persistent anti-dsDNA antibodies

Exclusion Criteria:

  1. Severe concomitant disease or organ damage

    • renal: renal insufficiency with glomerular filtration rate below 40ml/min
    • cardiac: congestive heart failure, LVEF < 40% determined by echocardiogram, uncontrolled arrhythmia
    • pulmonary: mean pulmonary arterial pressure >50mmHg, DLCO < 40 % predicted
    • gastrointestinal: liver cirrhosis; SGOT, SGPT greater than 2 x the upper limit of normal, unless due to active lupus
  2. Ongoing cancer or history of malignancy within 5 years of screening
  3. Women who are pregnant or breastfeeding or use non-reliable methods of contraception
  4. Subjects with active systemic infection
  5. Subjects with history of active viral infection within 6 months prior to screening, known HIV-infection or chronic Hepatitis B or Hepatitis C
  6. History of allergic reaction to cyclophosphamide, G-CSF or ATG
  7. Use of immunosuppressive agents for indications other than SLE
  8. Any comorbidity that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Transplantation of purified CD34+ autologous hematopoietic stem cells mobilized with cyclophosphamide (200mg/m2)and G-CSF (10µg/kg/d) after immunoablation with cyclophosphamide (200mg/kg)and rabbit-antithymocyteglobulin (90mg/kg)
Active Comparator: 2
Best currently available immunosuppressive/immunomodulatory therapy
Procedure: Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Transplantation of purified CD34+ autologous hematopoietic stem cells mobilized with cyclophosphamide (200mg/m2)and G-CSF (10µg/kg/d) after immunoablation with cyclophosphamide (200mg/kg)and rabbit-antithymocyteglobulin (90mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
SLEDAI
Time Frame: 48 months
48 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Serologic response (autoantibodies)
Time Frame: 48 months
48 months
Immune Reconstitution
Time Frame: 48 months
48 months
Organ-specific response parameters
Time Frame: 48 months
48 months

Collaborators and Investigators

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

Sponsor

Charite University, Berlin, Germany

Investigators

  • Principal Investigator: Falk Hiepe, Prof, Universitatsmedizin Charité

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

August 1, 2008

Primary Completion (Anticipated)

July 1, 2020

Study Completion (Anticipated)

August 1, 2020

Study Registration Dates

First Submitted

September 10, 2008

First Submitted That Met QC Criteria

September 10, 2008

First Posted (Estimate)

September 11, 2008

Study Record Updates

Last Update Posted (Actual)

March 20, 2017

Last Update Submitted That Met QC Criteria

March 17, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-1306

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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