Autoimmune DiseasesPhase 1/2ASTRADNCT00742300
Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases
A Phase 1/2 study testing Autologous hematopoietic stem cell transplantation in people with Autoimmune Diseases, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
While glucocorticoids and immunosuppressants ameliorate manifestations of autoimmune diseases 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- Autologous hematopoietic stem cell transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- Not given
- Where
- 1 siteGermany
- Study dates
- Jan 1998to not given
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Autoimmune disease
- Active disease with inadequate response to standard protocols (glucocorticoids and at least two different regimens of immunosuppressive drugs, such as intravenous cyclophosphamide 800-1000mg/application)
- Provision of informed consent by subject
Who cannot join
- Active or chronic infections
- Uncontrolled arrhythmia or congestive heart failure (ejection fraction below 50% determined by echocardiogram)
- Lung fibrosis (transfer factor for carbon monoxide [TLCO] <45%)
- renal insufficiency (glomerular filtration rate below 40 ml/min)
- Pulmonary arterial hypertension (>40mmHg)
- History of malignancy
- Women who are pregnant or breastfeeding
- Use non-reliable methods of contraception
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Open-Label Monocentric Clinical Trial for Induction of Tolerance With CD34-Enriched Autologous Hematopoietic Stem Cell Transplantation After High-Dose Chemotherapy With Cyclophosphamide and Rabbit-Antithymocyte Globulin for Refractory Autoimmune Diseases
While glucocorticoids and immunosuppressants ameliorate manifestations of autoimmune diseases 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 rationale for applying ASCT to autoimmune diseases has been the hope that immunoablation could eliminate inflammation-driving pathogenic cells from the immune system, and that regeneration of the patients' immune system from hematopoietic precursors could re-establish immunological tolerance.
- Conditions
- Autoimmune Diseases
- Being tested
- Autologous hematopoietic stem cell transplantation
- Keywords
- ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous hematopoietic stem cell transplantationProcedure or surgery
Also called Mobilization: 2.0 g/m2 Cyclophosphamide followed by daily G-CSF (10 µg/kg, Amgen, Thousand Oaks, CA), Conditioning: 200mg/kg Cyclophosphamide (Endoxan), 90mg/kg rabbit-antithymocyteglobulin (ATG, Fresenius, Bad Homburg, Germany), Stem cell selection: CliniMACS Device (Miltenyi Biotec, Bergisch Gladbach, Germany)
Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg)
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Treatment Group Receives: Procedure: Autologous hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Measured: 24 months
Overall Survival
Measured: 24 months
Secondary outcomes (3)
Immune Reconstitution
Measured: over 24 months
Organ-specific response parameters
Measured: 24 months
Serological Response (Autoantibodies)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2008 (estimated)
- Study startJan 1998
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Investigators
- Renate Arnold, Prof. Dr. med., Principal investigator, Charite University, Berlin, GermanyFalk Hiepe, Prof. Dr. med., Study chair, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00742300
- Sponsor's protocol ID
- CT-0198
- Acronym
- ASTRAD
- Status last verified
- Nov 2008
- First submitted
- 26 Aug 2008
- Last updated
- 24 Nov 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11056673Jayne 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.
PubMed 15119545Rosen O, Hiepe F, Massenkeil G, Thiel A, Arnold R. Relapse of systemic lupus erythematosus. Lancet. 2001 Mar 10;357(9258):807-8. doi: 10.1016/S0140-6736(05)71239-3. No abstract available.
PubMed 11254005Thiel 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.
PubMed 18292651Rosen O, Massenkeil G, Hiepe F, Pest S, Hauptmann S, Radtke H, Burmester G, Thiel A, Radbruch A, Heymer B, Arnold R. Cardiac death after autologous stem cell transplantation (ASCT) for treatment of systemic sclerosis (SSc): no evidence for cyclophosphamide-induced cardiomyopathy. Bone Marrow Transplant. 2001 Mar;27(6):657-8. doi: 10.1038/sj.bmt.1702829.
PubMed 11319598Alexander 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.
PubMed 18824594
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Open-Label Monocentric Clinical Trial for Induction of Tolerance With CD34-Enriched Autologous Hematopoietic Stem Cell Transplantation After High-Dose Chemotherapy With Cyclophosphamide and Rabbit-Antithymocyte Globulin for Refractory Autoimmune Diseases
- ClinicalTrials.gov ID
- NCT00742300
- Acronym / sponsor ID
- ASTRAD / CT-0198
- Conditions
- Autoimmune Diseases
- Keywords
- ASCT, Tolerance induction, SLE, Transplantation, Autoimmune diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Jan 1998
- First posted
- 27 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While glucocorticoids and immunosuppressants ameliorate manifestations of autoimmune diseases 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 rationale for applying ASCT to autoimmune diseases has been the hope that immunoablation could eliminate inflammation-driving pathogenic cells from the immune system, and that regeneration of the patients' immune system from hematopoietic precursors could re-establish immunological tolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Procedure: Autologous hematopoietic stem cell transplantationTreatment Group |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Autoimmune disease
- Active disease with inadequate response to standard protocols (glucocorticoids and at least two different regimens of immunosuppressive drugs, such as intravenous cyclophosphamide 800-1000mg/application)
- Provision of informed consent by subject
Key exclusion criteria (8 listed)
- Active or chronic infections
- Uncontrolled arrhythmia or congestive heart failure (ejection fraction below 50% determined by echocardiogram)
- Lung fibrosis (transfer factor for carbon monoxide [TLCO] <45%)
- renal insufficiency (glomerular filtration rate below 40 ml/min)
- Pulmonary arterial hypertension (>40mmHg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous hematopoietic stem cell transplantationAlso: Mobilization: 2.0 g/m2 Cyclophosphamide followed by daily G-CSF (10 µg/kg, Amgen, Thousand Oaks, CA), Conditioning: 200mg/kg Cyclophosphamide (Endoxan), 90mg/kg rabbit-antithymocyteglobulin (ATG, Fresenius, Bad Homburg, Germany), Stem cell selection: CliniMACS Device (Miltenyi Biotec, Bergisch Gladbach, Germany)Transplantation of CD34-selected autologous hematopoietic stem cells after high-dose chemotherapy with cyclophosphamide (200mg/kg) and rabbit-antithymocyteglobulin (90mg/kg) | Procedure or surgery | A |
Primary outcome
Disease-free survival
Time frame: 24 months
Overall Survival
Time frame: 24 months
3 secondary outcomes
Immune Reconstitution
Time frame: over 24 months
Organ-specific response parameters
Time frame: 24 months
Serological Response (Autoantibodies)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2008.
- Results publication: PubMed 11056673Rosen 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 publication: PubMed 15119545Jayne 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 publication: PubMed 11254005Rosen O, Hiepe F, Massenkeil G, Thiel A, Arnold R. Relapse of systemic lupus erythematosus. Lancet. 2001 Mar 10;357(9258):807-8. doi: 10.1016/S0140-6736(05)71239-3. No abstract available.
- Results publication: PubMed 18292651Thiel 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 publication: PubMed 11319598Rosen O, Massenkeil G, Hiepe F, Pest S, Hauptmann S, Radtke H, Burmester G, Thiel A, Radbruch A, Heymer B, Arnold R. Cardiac death after autologous stem cell transplantation (ASCT) for treatment of systemic sclerosis (SSc): no evidence for cyclophosphamide-induced cardiomyopathy. Bone Marrow Transplant. 2001 Mar;27(6):657-8. doi: 10.1038/sj.bmt.1702829.
- Derived from this study: PubMed 18824594Alexander 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renate Arnold, Prof. Dr. med. principal investigator
Charite University, Berlin, Germany
Falk Hiepe, Prof. Dr. med. study chair
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous hematopoietic stem cell transplantation in people with Autoimmune Diseases, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00742300, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2008.