REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUSPhase 2/3ASTILNCT05063513
Autologous Stem Cell Transplantation: International Lupus Trial
A Phase 2/3 study testing Autologous Hematopoietic Stem Cell Transplantation and Rituximab in people with REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS, run by European Society for Blood and Marrow Transplantation at 1 site in France.
Trial summary
The purpose of this study is to evaluate remission induction therapy for refractory Lupus Erythematosus with autologous hematopoietic stem cell transplantation (AHSCT) versus Rituximab (anti CD20) followed by maintenance therapy with mycophenolate mofetil (MMF). Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2009to Jul 2017
- Phase
- Phase 2/3
- 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 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age between 16 and 60 years.
- Diagnosis of systemic lupus erythematosus (SLE) according to ACR-criteria with antinuclear antibodies positive (ANA) on at least 2 successive tests at 3 months interval plus disease duration of more than 5 years since the diagnosis or first time of intensive immunosuppressive drugs.
- Sustained or relapsed active BILAG A SLE with documented evidence of at least one visceral involvement or refractory SLE as defined by either:
- kidney involvement: with the criteria for lupus renal BILAG A and a creatinine clearance > 30 ml/min/m2, not explained by other causes than SLE activity with a renal biopsy of less than 12 months showing a class III or IV lupus nephritis
- Any other type of vital organ involvement except mesenteric vasculitis with BILAG neurologic category A, cardiovascular or pulmonary category A, vasculitis category A
- Auto-immune cytopenias (hemolytic anemia and/or thrombo-cytopenia) defined as BILAG hematologic category A and confirmed by a bone marrow aspirate
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- Secondary antiphospholipid syndrome (SAPL) active despite full (INR > 3) anticoagulation after at least 6 months of the best standard local therapy using CY or MMF either alone or successively according to:
- the short term Eurolupus protocol low dose CY regimen of 6 x 500 mg iv CY at 2 weeks interval or
- the conventional treatment with 0.75 g/m2/month x 6 iv cyclophosphamide or
- MMF at 2 g daily for 3 to 6 months plus oral steroids above 0.5 mg/kg/day and be corticosteroids dependent and unable to decrease below 20 mg/day.
- Negative pregnancy test for women of child bearing age.
- Written informed consent.
Who cannot join
- Pregnancy, breast feeding or unwillingness to use adequate contraception methods during study (see 7.5).
- Severe concomitant disease:
- Respiratory: mean PAP > 50 mmHg (by cardiac echo or right heart catheterization), DLCO < 40% predicted, respiratory failure as defined by a resting arterial oxygen tension (PaO2) < 70 mmHg) and/or resting arterial carbon dioxide tension (PaCO2)> 50 mmHg) without oxygen supply
- Renal: creatinine clearance < 30 ml/min
- Cardiac: clinical evidence of congestive heart failure; LVEF < 40% (cardiac echo or multigated radionuclide angiography (MUGA)); > 1 cm pericardial effusion on cardiac echography; uncontrolled ventricular arrhythmia.
- Liver failure defined as a transaminases levels (ASAT, ALAT > 2 normal) unless related to activity of the disease.
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- Severe psychiatric disorders, including severe psychosis related to SLE disease that may prevent the ability to sign informed consent or undergo the procedure.
- Concurrent neoplasms or myelodysplasia except for localized basal cell carcinoma or squamous skin cancer or in situ cervical carcinoma of the uterus.
- Bone marrow insufficiency defined as neutropenia < 0.5 x 109/l, thrombo- cytopenia < 30 x 109/l, anaemia < 8 g/dl, CD4+ T lymphopenia < 200 x 106/l.
- Uncontrolled acute or chronic infection, including HIV, HTLV-1, 2 positivity, Hepatitis B surface Ag positive, hepatitis C PCR positive.
- Previous treatments with TLI, TBI or alkylating agents including cyclophosphamide > 15 g cumulative.
- Intracranial hematoma or previous bleeding documented within 30 days of the screening visit.
- Mesenteric vasculitis or ongoing gastrointestinal bleeding.
- Poor compliance of the patient as assessed by the referring physicians.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Remission Induction Therapy for Refractory Systemic Lupus Erythematosus With Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Versus Rituximab (antiCD20) Followed by Maintenance Therapy With Mycophenolate Mofetil (MMF)
The purpose of this study is to evaluate remission induction therapy for refractory Lupus Erythematosus with autologous hematopoietic stem cell transplantation (AHSCT) versus Rituximab (anti CD20) followed by maintenance therapy with mycophenolate mofetil (MMF).
Read the detailed description
To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (experimental arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus refractory to treatment with Cyclophosphamide and/or MMF alone plus steroids.
Secondary Objectives
- To evaluate the safety of AHSCT therapy versus rituximab (anti CD20) (control arm) with maintenance therapy by Mycophenolate Mofetil according to treatment related mortality and toxicity up to two years after randomization
- To evaluate the long term efficacy in the study arms according to repeated measures of Disease Activity and Damage scores, Quality of Life, the presence of other co morbidities, the daily dose of steroids rated quarterly up to two years after randomization.
- To evaluate in the study arms whether remission and disease activity correlates with immunological parameters, including immune reconstitution and auto antibodies
Trial Design:
Based on the existing European (28) and North American experience (29-31) of AHSCT in SLE, it is logical to suggest the following phase IIb trial designed in patients with severe refractory SLE after at least 6 months of best standard local therapy using either alone or successively according to current international clinical consensus as follows:
- the short term Eurolupus protocol low dose CY regimen of 6 x 500 mg iv cyclophosphamide at 2 weeks interval or
- the conventional treatment with 0.75 g/m2/month x 6 iv cyclophosphamide or
- mycophenolate mofetil at 2 g/daily for 3 to 6 months plus oral steroids above 0.5 mg/kg/day and unable to decrease below 20 mg/day.
All patients will be randomised at time of inclusion in one of two groups:
- Group A (experimental arm) will undergo mobilisation with CY 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
- Group B (control arm) will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
- Conditions
- REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Rituximab
- Keywords
- Lupus, Transplant, Rituximab, Mycophenolate Mofetil, Autologous Hematopoietic Stem Cell Transplantation, Refractory Systemic Lupus Erythematosus
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationBiological
Also called Cellcept for Mycophenolate Mofetil
Experimental arm will undergo mobilisation with CY 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
RituximabDrug
Also called MabThera for Rituximab, Cellcept for Mycophenolate Mofetil
Control arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
| Study group | Role | What they receive |
|---|---|---|
| Transplant arm | Experimental | Experimental arm will undergo mobilisation with cyclophosphamide (CY) 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. Receives: Biological: Autologous Hematopoietic Stem Cell Transplantation |
| Rituximab arm | Active comparator | Control arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (study arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus
The proportion of patients who achieve clinical success defined by combined renal and extra renal remission with independence from all other immunosuppressive agents other than MMF
Measured: 2 years
Secondary outcomes (6)
Treatment completion
the ability to complete the assigned treatment regimen including the AHSCT procedure plus then to comply with maintenance therapy by MMF up to 24 months after the randomization (independently of achieving clinical success).
Measured: 5 years
Clinical success
combined renal and extra renal remission, such as neither the persistence nor the increase in disease activity in any organ system requiring a change in therapy (BILAG A scores) plus independence from all immunosupressive agents but MMF assigned by the study for maintenance other than low dose prednisone (< 10 mg daily on average daily dose)
Measured: 5 years
Disease activity
BILAG (from 0 to 72) and the SLEDAI (from 0 to 105) index scores
Measured: 5 years
Disease damage
SLICC/ACRR Damage Index (from 0 to 47) for SLE
Measured: 5 years
Quality of Life
SF 36
Measured: 5 years
The number of relapses
an increase in disease activity in any organ system requiring a change in therapy (BILAG A scores)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study startJul 2009
- Primary completionJul 2013
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUSStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- EULAR
- Responsible party
- Sponsor
- Investigators
- Dominique Farge, MD, Study chair, Dept. of Internal Medicine, Hôpital Saint-Louis, 1 Avenue ClaudeVellefaux, F-75475ParisCédex 10, France.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063513
- Sponsor's protocol ID
- 2008-ADWP-01
- Other IDs
- EUdraCT No: 2008-006090-32
- Acronym
- ASTIL
- Status last verified
- Sep 2023
- First submitted
- 6 May 2009
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remission Induction Therapy for Refractory Systemic Lupus Erythematosus With Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Versus Rituximab (antiCD20) Followed by Maintenance Therapy With Mycophenolate Mofetil (MMF)
- ClinicalTrials.gov ID
- NCT05063513
- Acronym / sponsor ID
- ASTIL / 2008-ADWP-01
- Conditions
- REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS
- Keywords
- Lupus, Transplant, Rituximab, Mycophenolate Mofetil, Autologous Hematopoietic Stem Cell Transplantation, Refractory Systemic Lupus Erythematosus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- EULAR
- Study start
- Jul 2009
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 1 Oct 2021 (actual)
- 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.
The purpose of this study is to evaluate remission induction therapy for refractory Lupus Erythematosus with autologous hematopoietic stem cell transplantation (AHSCT) versus Rituximab (anti CD20) followed by maintenance therapy with mycophenolate mofetil (MMF).
Detailed description
To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (experimental arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus refractory to treatment with Cyclophosphamide and/or MMF alone plus steroids.
Secondary Objectives
- To evaluate the safety of AHSCT therapy versus rituximab (anti CD20) (control arm) with maintenance therapy by Mycophenolate Mofetil according to treatment related mortality and toxicity up to two years after randomization
- To evaluate the long term efficacy in the study arms according to repeated measures of Disease Activity and Damage scores, Quality of Life, the presence of other co morbidities, the daily dose of steroids rated quarterly up to two years after randomization.
- To evaluate in the study arms whether remission and disease activity correlates with immunological parameters, including immune reconstitution and auto antibodies
Trial Design:
Based on the existing European (28) and North American experience (29-31) of AHSCT in SLE, it is logical to suggest the following phase IIb trial designed in patients with severe refractory SLE after at least 6 months of best standard local therapy using either alone or successively according to current international clinical consensus as follows:
- the short term Eurolupus protocol low dose CY regimen of 6 x 500 mg iv cyclophosphamide at 2 weeks interval or
- the conventional treatment with 0.75 g/m2/month x 6 iv cyclophosphamide or
- mycophenolate mofetil at 2 g/daily for 3 to 6 months plus oral steroids above 0.5 mg/kg/day and unable to decrease below 20 mg/day.
All patients will be randomised at time of inclusion in one of two groups:
- Group A (experimental arm) will undergo mobilisation with CY 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
- Group B (control arm) will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transplant arm | Experimental | Biological: Autologous Hematopoietic Stem Cell TransplantationExperimental arm will undergo mobilisation with cyclophosphamide (CY) 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. |
| Rituximab arm | Active comparator | Drug: RituximabControl arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Age between 16 and 60 years.
- Diagnosis of systemic lupus erythematosus (SLE) according to ACR-criteria with antinuclear antibodies positive (ANA) on at least 2 successive tests at 3 months interval plus disease duration of more than 5 years since the diagnosis or first time of intensive immunosuppressive drugs.
- Sustained or relapsed active BILAG A SLE with documented evidence of at least one visceral involvement or refractory SLE as defined by either:
- Negative pregnancy test for women of child bearing age.
- Written informed consent.
Key exclusion criteria (14 listed)
- Pregnancy, breast feeding or unwillingness to use adequate contraception methods during study (see 7.5).
- Severe concomitant disease:
- Liver failure defined as a transaminases levels (ASAT, ALAT > 2 normal) unless related to activity of the disease.
- Severe psychiatric disorders, including severe psychosis related to SLE disease that may prevent the ability to sign informed consent or undergo the procedure.
- Concurrent neoplasms or myelodysplasia except for localized basal cell carcinoma or squamous skin cancer or in situ cervical carcinoma of the uterus.
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: Cellcept for Mycophenolate MofetilExperimental arm will undergo mobilisation with CY 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. | Biological | Transplant arm |
| RituximabAlso: MabThera for Rituximab, Cellcept for Mycophenolate MofetilControl arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization. | Drug | Rituximab arm |
Primary outcome
To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (study arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus
Time frame: 2 years
The proportion of patients who achieve clinical success defined by combined renal and extra renal remission with independence from all other immunosuppressive agents other than MMF
6 secondary outcomes
Treatment completion
Time frame: 5 years
Clinical success
Time frame: 5 years
Disease activity
Time frame: 5 years
Disease damage
Time frame: 5 years
Quality of Life
Time frame: 5 years
The number of relapses
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
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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.
Dominique Farge, MD study chair
Dept. of Internal Medicine, Hôpital Saint-Louis, 1 Avenue ClaudeVellefaux, F-75475ParisCédex 10, France.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Autologous Hematopoietic Stem Cell Transplantation and Rituximab in people with REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS, run by European Society for Blood and Marrow Transplantation at 1 site in France.
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 12 inclusion and 14 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: withdrawn, as of the sponsor's last update on 13 Sep 2023. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (study arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Sep 2023.