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

NCT ID: NCT00750971

Last Updated: 2017-03-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2020-08-31

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Immunoablation and Autologous Hematopoietic Stem Cell Transplantation

Group Type: EXPERIMENTAL

Immunoablation and Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

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)

2

Best currently available immunosuppressive/immunomodulatory therapy

Group Type: ACTIVE_COMPARATOR

Immunoablation and Autologous Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

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)

Interventions

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)

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Falk Hiepe

Prof. Dr. Falk Hiepe

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Falk Hiepe, Prof

Role: PRINCIPAL_INVESTIGATOR

Universitätsmedizin Charité

Locations

Universitätsmedizin Charité

Berlin, , Germany

Site Status: RECRUITING

Universitätsklinik Köln

Cologne, , Germany

Site Status: RECRUITING

Universitätsklinik Düsseldorf

Düsseldorf, , Germany

Site Status: RECRUITING

Universitätsklinikum Essen

Essen, , Germany

Site Status: RECRUITING

Universitätsklinik Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Universitäsklinik Mainz

Mainz, , Germany

Site Status: RECRUITING

Universitätsklinik Tübingen

Tübingen, , Germany

Site Status: RECRUITING

Universitätsklinik Würzburg

Würzburg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Falk Hiepe, Prof.

Role: CONTACT

falk.hiepe@charite.de

+49 30 450 513026

Renate Arnold, Prof.

Role: CONTACT

renate.arnold@charite.de

+49 30 450-553-302

Facility Contacts

Falk Hiepe, Prof

Role: primary

+49 30 450 513026

Andrea Rubbert-Roth, PD

Role: primary

+49 (0) 221-4783993

Mathias Schneider, Prof.

Role: primary

+49 (0) 211-8117817

Christoph Specker, Prof.

Role: primary

+49 (0)201-84081214

Hanns-Marting Lorenz, Prof.

Role: primary

+49 (0) 6221-568044

Karin Kolbe, MD

Role: primary

Ina Kötter, PD

Role: primary

+49 (0) 7071-2984095

Hans-Peter Tony, Prof.

Role: primary

+49 (0) 931-20170420

References

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.

Reference Type: BACKGROUND

PMID: 18292651 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15119545 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11056673 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18824594 (View on PubMed)

Other Identifiers

CT-1306

Identifier Type: -

Identifier Source: org_study_id