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EBMT ADWP Prospective Non-interventional Study: Post-AHSCT Management in SSC Patients (NISSC-2) (NISSC-2)

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ClinicalTrials.gov Identifier: NCT03444805
Recruitment Status : Recruiting
First Posted : February 23, 2018
Last Update Posted : September 2, 2019
Sponsor:
Information provided by (Responsible Party):
European Group for Blood and Marrow Transplantation

Tracking Information
First Submitted Date February 19, 2018
First Posted Date February 23, 2018
Last Update Posted Date September 2, 2019
Actual Study Start Date July 1, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 22, 2018)
Progression free survival (PFS), [ Time Frame: 2 years post transplant ]
defined as survival since AHSCT without evidence of progression of SSc.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03444805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: February 22, 2018)
  • Treatment related toxicity [ Time Frame: 100 days post-transplant ]
    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).
  • 100 days Treatment Related Mortality (100d TRM) [ Time Frame: 100 days post-transplant ]
    defined as any death during 100 days following transplant that cannot be attributed to progression or relapse of the disease
  • Overall Survival (OS) [ Time Frame: 2 years post-transplant ]
    Overall survival
  • Use of prednisone equivalent [ Time Frame: 1 year and 2 years post-transplant ]
    Use of prednisolone equivalent > 6 mg/day for more than 3 months
  • Use of immunosuppressive drugs [ Time Frame: 2 years post-transplant ]
    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)
  • Use of post-transplant biotherapies [ Time Frame: 2 years post-transplant ]
    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)
  • Response to treatment [ Time Frame: 1 year and 2 years post-transplant ]
    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)
  • Infectious complications, CMV / EBV reactivation [ Time Frame: 2 years post-transplant ]
    Infectious complications, CMV / EBV reactivation
  • Secondary autoimmune diseases and secondary malignancy [ Time Frame: 2 years post-transplant ]
    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
  • Immune reconstitution [ Time Frame: 2 years post-transplant ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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)
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres
Condition Autoimmune Diseases
Intervention Procedure: Autologous HSCT
1st AHSCT
Study Groups/Cohorts NISSC-2
SSC patients treated with AHSCT
Intervention: Procedure: Autologous HSCT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 22, 2018)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 30, 2023
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Manuela Badoglio, MS +33 1 70 64 24 16 manuela.badoglio@upmc.fr
Contact: Dominique Farge, PhD dominique.farge-bancel@aphp.fr
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03444805
Other Study ID Numbers ADWP 8410025
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party European Group for Blood and Marrow Transplantation
Study Sponsor European Group for Blood and Marrow Transplantation
Collaborators Not Provided
Investigators
Study Chair: Dominique Farge, PhD EBMT ADWP
PRS Account European Group for Blood and Marrow Transplantation
Verification Date August 2019