Autoimmune DiseasesNISSC-2NCT03444805
EBMT ADWP Prospective Non-interventional Study: Post-AHSCT Management in SSC Patients (NISSC-2)
An observational study of Autoimmune Diseases, run by European Society for Blood and Marrow Transplantation at 1 site in France.
Trial summary
The aim of the study is to assess the effectiveness of various post-transplant treatment management approaches on clinical and immune biological responses after Autologous Hematopoietic Stem Cell transplantation (AHSCT) for Systemic Sclerosis (SSc) as currently performed by the different treatment protocols used in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- Autologous HSCT
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jul 2019to 30 Mar 2023
- Phase
- Observational
- 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 years and older
- All sexes
- Adult, Older adult
Study population: All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres
Who may be able to join
- - Autologous HSCT
- - Age above 18 years at time of transplant.
- -. Established diagnosis of progressive SSc according to 2013 ACR/EULAR classification criteria
Who cannot join
- Pregnancy or inadequate contraception
- Severe concomitant disease
- Reduced lung, cardiac or renal function
- .Reduced lung function with FVC < 50% or DLCO < 30% (of predicted values) b; .Pulmonary arterial hypertension with baseline (resting) PASP > 40 mmHg or mPAP > 25 mmHg or a PASP > 45 mmHg or mPAP > 30 mmHg after fluid challenge or Pulmonary vascular resistance > 3 Wood units on RHC c. Severe heart failure with Ejection Fraction < 45% by cardiac echocardiography d. D-sign of septal bounce on cardiac MRI e. Unrevascularized severe coronary artery disease f. Untreated severe arrhythmia g. Cardiac tamponade h. Constrictive pericarditis i. Kidney insufficiency: creatinine clearance <30ml/min Previously damaged bone marrow
- Leukopenia < 2.0 x 109/L (total white cell count)
- Thrombocytopenia < 100 x 109/L
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- Uncontrolled severe or chronic infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, tuberculosis)
- Severe concomitant psychiatric illness (depression, psychosis)
- Concurrent neoplasms or myelodysplasia in the past 5 years
- Smoking (current)
Trial locations and contacts
1 site in 1 country.
Dominique Farge, PhD contact
France1 site, 1 recruiting
- Recruiting
Badoglio Manuela- EBMT Paris Office
Paris, 75010
Manuela Badoglio, +33.1.70.64.24.16, manuela.badoglio@upmc.fr
Dominique Farge, PhD, +33 (0)1 40 27 46 13, dominique.farge-bancel@sls.aphp.fr
About this study
Official title: Post-AHSCT (Autologous Hematopoietic Stem Cell Transplantation) Management for Patients With Systemic Sclerosis: a Prospective, Non-interventional Approach Across Europe (NISSC-2) for the Autoimmune Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
The aim of the study is to assess the effectiveness of various post-transplant treatment management approaches on clinical and immune biological responses after Autologous Hematopoietic Stem Cell transplantation (AHSCT) for Systemic Sclerosis (SSc) as currently performed by the different treatment protocols used in routine clinical practice across Europe in various EBMT centres
Read the detailed description
NISSc-2 is a prospective observational study specifically designed to assess the effectiveness of various post-transplant treatment management approaches on clinical and immune biological responses after Autologous Hematopoietic Stem Cell transplantation (AHSCT) for Systemic Sclerosis (SSc) as currently performed by the different treatment protocols used in routine clinical practice across Europe in various EBMT centres through the careful recording and analysis of routinely collected clinical and immune biological data, and specific data regarding post-transplant use of SSc active treatments, including:
- Steroids,
- SSc active treatments after AHSCT such as mycophenolate mofetil (MMF), azathioprine, cyclophosphamide (oral or IV), methotrexate, polyclonal antibodies (such as ATG) or monoclonal antibodies (rituximab, belimumab or any others) as well as their respective dosage and duration of each treatment. These post-transplant treatments can be administered for various reasons, which can be specified by local investigators, such as per local protocol decision for maintenance therapy, or for disease progression with or without prior clinical response, during routine clinical follow-up. Patients who do not receive any post-transplant therapy will also be observed.
Different protocols are used in the different centres, but it is not yet clear, which approach will be the most efficient and the safest. The role of stem cell purification with CD34-selection also needs to be determined prospectively.
In addition, the EBMT Autoimmune Diseases and Immunobiology Working Parties developed and implemented guidelines for 'good laboratory practice' in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after AHSCT [16]. To follow post-transplant immune reconstitution according to ADWP GCP, results of routine analyses performed by centres under standardized conditions on available biological samples will be investigated in correlation to clinical outcome parameters. Every centre will follow its own local protocol for AHSCT, which usually refers to the recent update of the EBMT guidelines for AHSCT in autoimmune disease.
We therefore specifically designed NISCC-II to prospectively capture various post-ASHCT management protocols and their effect on the observed clinical response after AHSCT.
- Conditions
- Autoimmune Diseases
- Being tested
- Autologous HSCT
- Keywords
- Autoimmune diseases, Systemic sclerosis, Autologous hematopoietic stem cell transplant (AHSCT), Post-AHSCT management, Immune reconstitution
- Medical subject headings
- Autoimmune Diseases, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous HSCTProcedure or surgery
1st AHSCT
| Study group | Role | What they receive |
|---|---|---|
| NISSC-2 | SSC patients treated with AHSCT Receives: Procedure: Autologous HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS),
defined as survival since AHSCT without evidence of progression of SSc.
Measured: 2 years post transplant
Secondary outcomes (10)
Treatment related toxicity
Treatment related toxicity throughout the study period using WHO toxicity parameters (expressed as maximum grade toxicity per organ system, see appendix) Incidence of Adverse Events (AE) and Serious Adverse Events (SE) Neutrophil and platelet engraftment, defined as first day after transplantation with absolute neutrophil count > 0.5 x 109/L and platelet count >20 x 109/L (without platelet transfusion).
Measured: 100 days post-transplant
100 days Treatment Related Mortality (100d TRM)
defined as any death during 100 days following transplant that cannot be attributed to progression or relapse of the disease
Measured: 100 days post-transplant
Overall Survival (OS)
Overall survival
Measured: 2 years post-transplant
Use of prednisone equivalent
Use of prednisolone equivalent > 6 mg/day for more than 3 months
Measured: 1 year and 2 years post-transplant
Use of immunosuppressive drugs
defined as use of any post-transplant immunosuppressive drugs (mycophenolate mofetil, azathioprine, oral or iv cyclosphosphamide or methotrexate) for either causes (maintenance therapy as per local protocol decision, SSc progression or relapse) and total duration of exposure to this post-transplant immunosuppressive treatment (average monthly daily dose and months duration)
Measured: 2 years post-transplant
Use of post-transplant biotherapies
defined as use of any monoclonal (i.e. anti CD20, anti-BLyS, alemtuzumab or polyclonal (i.e. ATG) antibodies for either causes (per local protocol decision, EBV infection or reactivation, progression or relapse) and total doses (in number and g/kg)
Measured: 2 years post-transplant
Response to treatment
defined as any of the following changes
- 25% improvement in mRSS and/or
- ≥10% improvement in DLCO or FVC as compared to baseline (before mobilisation)
Measured: 1 year and 2 years post-transplant
Infectious complications, CMV / EBV reactivation
Infectious complications, CMV / EBV reactivation
Measured: 2 years post-transplant
Secondary autoimmune diseases and secondary malignancy
defined, autoimmune thrombocytopaenia, autoimmune thyroid disease, autoimmune haemolytic anaemia, Evans' syndrome, acquired haemophila, ulcerative colitis, rheumatoid arthritis and spondyloarthropathy, autoimmune hepatitis, others) and secondary malignancy (EBV lymphoproliferative disorders, AML, MDS, skin cancers, and any others
Measured: 2 years post-transplant
Immune reconstitution
Results of routine analysis performed by centres will be investigated in correlation to clinical outcomes parameters and will allow to follow post-transplant immune reconstitution according to ADWP GCP.
Measured: 2 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2018
- Study start1 Jul 2019
- Primary completion31 Dec 2021 (estimated)
- Study completion30 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune DiseasesStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Dominique Farge, PhD, Study chair, EBMT ADWP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03444805
- Sponsor's protocol ID
- ADWP 8410025
- Acronym
- NISSC-2
- Status last verified
- Aug 2019
- First submitted
- 19 Feb 2018
- Last updated
- 3 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-AHSCT (Autologous Hematopoietic Stem Cell Transplantation) Management for Patients With Systemic Sclerosis: a Prospective, Non-interventional Approach Across Europe (NISSC-2) for the Autoimmune Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
- ClinicalTrials.gov ID
- NCT03444805
- Acronym / sponsor ID
- NISSC-2 / ADWP 8410025
- Conditions
- Autoimmune Diseases
- Keywords
- Autoimmune diseases, Systemic sclerosis, Autologous hematopoietic stem cell transplant (AHSCT), Post-AHSCT management, Immune reconstitution
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 30 Mar 2023 (estimated)
- First posted
- 23 Feb 2018 (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 aim of the study is to assess the effectiveness of various post-transplant treatment management approaches on clinical and immune biological responses after Autologous Hematopoietic Stem Cell transplantation (AHSCT) for Systemic Sclerosis (SSc) as currently performed by the different treatment protocols used in routine clinical practice across Europe in various EBMT centres
Detailed description
NISSc-2 is a prospective observational study specifically designed to assess the effectiveness of various post-transplant treatment management approaches on clinical and immune biological responses after Autologous Hematopoietic Stem Cell transplantation (AHSCT) for Systemic Sclerosis (SSc) as currently performed by the different treatment protocols used in routine clinical practice across Europe in various EBMT centres through the careful recording and analysis of routinely collected clinical and immune biological data, and specific data regarding post-transplant use of SSc active treatments, including:
- Steroids,
- SSc active treatments after AHSCT such as mycophenolate mofetil (MMF), azathioprine, cyclophosphamide (oral or IV), methotrexate, polyclonal antibodies (such as ATG) or monoclonal antibodies (rituximab, belimumab or any others) as well as their respective dosage and duration of each treatment. These post-transplant treatments can be administered for various reasons, which can be specified by local investigators, such as per local protocol decision for maintenance therapy, or for disease progression with or without prior clinical response, during routine clinical follow-up. Patients who do not receive any post-transplant therapy will also be observed.
Different protocols are used in the different centres, but it is not yet clear, which approach will be the most efficient and the safest. The role of stem cell purification with CD34-selection also needs to be determined prospectively.
In addition, the EBMT Autoimmune Diseases and Immunobiology Working Parties developed and implemented guidelines for 'good laboratory practice' in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after AHSCT [16]. To follow post-transplant immune reconstitution according to ADWP GCP, results of routine analyses performed by centres under standardized conditions on available biological samples will be investigated in correlation to clinical outcome parameters. Every centre will follow its own local protocol for AHSCT, which usually refers to the recent update of the EBMT guidelines for AHSCT in autoimmune disease.
We therefore specifically designed NISCC-II to prospectively capture various post-ASHCT management protocols and their effect on the observed clinical response after AHSCT.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NISSC-2 | – | Procedure: Autologous HSCTSSC patients treated with AHSCT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres
Key inclusion criteria (3 listed)
- - Autologous HSCT
- - Age above 18 years at time of transplant.
- -. Established diagnosis of progressive SSc according to 2013 ACR/EULAR classification criteria
Key exclusion criteria (10 listed)
- Pregnancy or inadequate contraception
- Severe concomitant disease
- Reduced lung, cardiac or renal function
- Uncontrolled severe or chronic infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, tuberculosis)
- Severe concomitant psychiatric illness (depression, psychosis)
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 HSCT1st AHSCT | Procedure or surgery | NISSC-2 |
Primary outcome
Progression free survival (PFS),
Time frame: 2 years post transplant
defined as survival since AHSCT without evidence of progression of SSc.
10 secondary outcomes
Treatment related toxicity
Time frame: 100 days post-transplant
100 days Treatment Related Mortality (100d TRM)
Time frame: 100 days post-transplant
Overall Survival (OS)
Time frame: 2 years post-transplant
Use of prednisone equivalent
Time frame: 1 year and 2 years post-transplant
Use of immunosuppressive drugs
Time frame: 2 years post-transplant
Use of post-transplant biotherapies
Time frame: 2 years post-transplant
Response to treatment
Time frame: 1 year and 2 years post-transplant
Infectious complications, CMV / EBV reactivation
Time frame: 2 years post-transplant
Secondary autoimmune diseases and secondary malignancy
Time frame: 2 years post-transplant
Immune reconstitution
Time frame: 2 years post-transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2019.
- Organisation websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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, PhD contact
Dominique Farge, PhD study chair
EBMT ADWP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmune Diseases, 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 3 inclusion and 10 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 3 Sep 2019. 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.
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?
Contact Manuela Badoglio, MS (+33 1 70 64 24 16, manuela.badoglio@upmc.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS), (time frame: 2 years post transplant). 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 3 Sep 2019.