Clinical trial NCT03444805: EBMT ADWP Prospective Non-interventional Study: Post-AHSCT Management in SSC Patients (NISSC-2)
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)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Autoimmune Diseases
Keywords: Autoimmune diseases
Systemic sclerosis
Autologous hematopoietic stem cell transplant (AHSCT)
Post-AHSCT management
Immune reconstitution
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
First posted: 2018-02-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. - Autologous HSCT
2. - Age above 18 years at time of transplant.
3. -. Established diagnosis of progressive SSc according to 2013 ACR/EULAR classification criteria

Exclusion Criteria:

1. Pregnancy or inadequate contraception
2. Severe concomitant disease
3. Reduced lung, cardiac or renal function

   a. .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
   1. Leukopenia \< 2.0 x 109/L (total white cell count)
   2. Thrombocytopenia \< 100 x 109/L
4. Uncontrolled severe or chronic infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, tuberculosis)
5. Severe concomitant psychiatric illness (depression, psychosis)
6. Concurrent neoplasms or myelodysplasia in the past 5 years
7. Smoking (current)

Primary outcomes:
measure: Progression free survival (PFS),
timeFrame: 2 years post transplant
Secondary outcomes:
measure: Treatment related toxicity
timeFrame: 100 days post-transplant
measure: 100 days Treatment Related Mortality (100d TRM)
timeFrame: 100 days post-transplant
measure: Overall Survival (OS)
timeFrame: 2 years post-transplant
measure: Use of prednisone equivalent
timeFrame: 1 year and 2 years post-transplant
measure: Use of immunosuppressive drugs
timeFrame: 2 years post-transplant
measure: Use of post-transplant biotherapies
timeFrame: 2 years post-transplant
measure: Response to treatment
timeFrame: 1 year and 2 years post-transplant
measure: Infectious complications, CMV / EBV reactivation
timeFrame: 2 years post-transplant
measure: Secondary autoimmune diseases and secondary malignancy
timeFrame: 2 years post-transplant
measure: Immune reconstitution
timeFrame: 2 years post-transplant
Other outcomes:
Locations:
city: Paris
country: France
facility: Badoglio Manuela- EBMT Paris Office
Study officials:
affiliation: EBMT ADWP
name: Dominique Farge, PhD
role: STUDY_CHAIR
References: