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

Primary Purpose

Systemic Lupus Erythematosus

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring ASSIST, SLE, Stem Cell Transplantation, Tolerance

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Universitätsmedizin CharitéRecruiting
  • Universitätsklinik DüsseldorfRecruiting
  • Universitätsklinikum EssenRecruiting
  • Universitätsklinik HeidelbergRecruiting
  • Universitätsklinik KölnRecruiting
  • Universitäsklinik MainzRecruiting
  • Universitätsklinik TübingenRecruiting
  • Universitätsklinik WürzburgRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Immunoablation and Autologous Hematopoietic Stem Cell Transplantation

Best currently available immunosuppressive/immunomodulatory therapy

Outcomes

Primary Outcome Measures

SLEDAI

Secondary Outcome Measures

Serologic response (autoantibodies)
Immune Reconstitution
Organ-specific response parameters

Full Information

First Posted
September 10, 2008
Last Updated
March 17, 2017
Sponsor
Charite University, Berlin, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00750971
Brief Title
Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)
Acronym
ASSIST
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
August 2008 (undefined)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
ASSIST, SLE, Stem Cell Transplantation, Tolerance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Arm Title
2
Arm Type
Active Comparator
Arm Description
Best currently available immunosuppressive/immunomodulatory therapy
Intervention Type
Procedure
Intervention Name(s)
Immunoablation and Autologous Hematopoietic Stem Cell Transplantation
Intervention Description
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)
Primary Outcome Measure Information:
Title
SLEDAI
Time Frame
48 months
Secondary Outcome Measure Information:
Title
Serologic response (autoantibodies)
Time Frame
48 months
Title
Immune Reconstitution
Time Frame
48 months
Title
Organ-specific response parameters
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria Age between 18 and 60 years, inclusive Provision of informed consent 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: 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 Ongoing cancer or history of malignancy within 5 years of screening Women who are pregnant or breastfeeding or use non-reliable methods of contraception Subjects with active systemic infection Subjects with history of active viral infection within 6 months prior to screening, known HIV-infection or chronic Hepatitis B or Hepatitis C History of allergic reaction to cyclophosphamide, G-CSF or ATG Use of immunosuppressive agents for indications other than SLE Any comorbidity that in the opinion of the investigator would jeopardize the ability of the subject to tolerate therapy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Falk Hiepe, Prof.
Phone
+49 30 450 513026
Email
falk.hiepe@charite.de
First Name & Middle Initial & Last Name or Official Title & Degree
Renate Arnold, Prof.
Phone
+49 30 450-553-302
Email
renate.arnold@charite.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Falk Hiepe, Prof
Organizational Affiliation
Universitätsmedizin Charité
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsmedizin Charité
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Falk Hiepe, Prof
Phone
+49 30 450 513026
First Name & Middle Initial & Last Name & Degree
Falk Hiepe, Prof.
Facility Name
Universitätsklinik Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathias Schneider, Prof.
Phone
+49 (0) 211-8117817
First Name & Middle Initial & Last Name & Degree
Mathias Schneider, Prof.
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45239 Essen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Specker, Prof.
Phone
+49 (0)201-84081214
First Name & Middle Initial & Last Name & Degree
Christoph Specker, Prof.
Facility Name
Universitätsklinik Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hanns-Marting Lorenz, Prof.
Phone
+49 (0) 6221-568044
First Name & Middle Initial & Last Name & Degree
Hanns-Martin Lorenz, Prof.
Facility Name
Universitätsklinik Köln
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Rubbert-Roth, PD
Phone
+49 (0) 221-4783993
First Name & Middle Initial & Last Name & Degree
Andrea Rubbert-Roth, PD
Facility Name
Universitäsklinik Mainz
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karin Kolbe, MD
First Name & Middle Initial & Last Name & Degree
Karin Kolbe, MD
Facility Name
Universitätsklinik Tübingen
City
Tübingen
ZIP/Postal Code
72026
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ina Kötter, PD
Phone
+49 (0) 7071-2984095
First Name & Middle Initial & Last Name & Degree
Ina Kötter, PD
Facility Name
Universitätsklinik Würzburg
City
Würzburg
ZIP/Postal Code
97070
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hans-Peter Tony, Prof.
Phone
+49 (0) 931-20170420
First Name & Middle Initial & Last Name & Degree
Hans-Peter Tony, Prof.

12. IPD Sharing Statement

Citations:
PubMed Identifier
18292651
Citation
Thiel A, Alexander T, Schmidt CA, Przybylski GK, Kimmig S, Kohler S, Radtke H, Gromnica-Ihle E, Massenkeil G, Radbruch A, Arnold R, Hiepe F. Direct assessment of thymic reactivation after autologous stem cell transplantation. Acta Haematol. 2008;119(1):22-7. doi: 10.1159/000117824. Epub 2008 Feb 22.
Results Reference
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PubMed Identifier
15119545
Citation
Jayne D, Passweg J, Marmont A, Farge D, Zhao X, Arnold R, Hiepe F, Lisukov I, Musso M, Ou-Yang J, Marsh J, Wulffraat N, Besalduch J, Bingham SJ, Emery P, Brune M, Fassas A, Faulkner L, Ferster A, Fiehn C, Fouillard L, Geromin A, Greinix H, Rabusin M, Saccardi R, Schneider P, Zintl F, Gratwohl A, Tyndall A; European Group for Blood and Marrow Transplantation; European League Against Rheumatism Registry. Autologous stem cell transplantation for systemic lupus erythematosus. Lupus. 2004;13(3):168-76. doi: 10.1191/0961203304lu525oa.
Results Reference
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PubMed Identifier
11056673
Citation
Rosen O, Thiel A, Massenkeil G, Hiepe F, Haupl T, Radtke H, Burmester GR, Gromnica-Ihle E, Radbruch A, Arnold R. Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res. 2000;2(4):327-36. doi: 10.1186/ar107. Epub 2000 Jun 8.
Results Reference
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PubMed Identifier
18824594
Citation
Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, Mei H, Radtke H, Gromnica-Ihle E, Burmester GR, Arnold R, Radbruch A, Hiepe F. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood. 2009 Jan 1;113(1):214-23. doi: 10.1182/blood-2008-07-168286. Epub 2008 Sep 29.
Results Reference
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Autologous Stem Cell Transplantation for Refractory Systemic Lupus Erythematosus (ASSIST)

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