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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

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

Condition or disease Intervention/treatment
Autoimmune Diseases Procedure: Autologous HSCT

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.


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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
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)
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : March 30, 2023

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
NISSC-2
SSC patients treated with AHSCT
Procedure: Autologous HSCT
1st AHSCT




Primary Outcome Measures :
  1. Progression free survival (PFS), [ Time Frame: 2 years post transplant ]
    defined as survival since AHSCT without evidence of progression of SSc.


Secondary Outcome Measures :
  1. 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).

  2. 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

  3. Overall Survival (OS) [ Time Frame: 2 years post-transplant ]
    Overall survival

  4. 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

  5. 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)

  6. 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)

  7. 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)

  8. Infectious complications, CMV / EBV reactivation [ Time Frame: 2 years post-transplant ]
    Infectious complications, CMV / EBV reactivation

  9. 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

  10. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03444805


Contacts
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Contact: Manuela Badoglio, MS +33 1 70 64 24 16 manuela.badoglio@upmc.fr
Contact: Dominique Farge, PhD dominique.farge-bancel@aphp.fr

Locations
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France
Badoglio Manuela- EBMT Paris Office Recruiting
Paris, France, 75010
Contact: Manuela Badoglio    +33.1.70.64.24.16    manuela.badoglio@upmc.fr   
Contact: Dominique Farge, PhD    +33 (0)1 40 27 46 13    dominique.farge-bancel@sls.aphp.fr   
Principal Investigator: Dominique Farge, PhD         
Sub-Investigator: Joerg Henes, MD         
Sub-Investigator: Hans Ulrich Scherer, PhD         
Sub-Investigator: John A Snowden, PhD         
Sub-Investigator: Nicoletta Del Papa, PhD         
Sub-Investigator: John Moore, PhD         
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Investigators
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Study Chair: Dominique Farge, PhD EBMT ADWP

Additional Information:
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Responsible Party: European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT03444805     History of Changes
Other Study ID Numbers: ADWP 8410025
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Group for Blood and Marrow Transplantation:
Autoimmune diseases
Systemic sclerosis
Autologous hematopoietic stem cell transplant (AHSCT)
Post-AHSCT management
Immune reconstitution
Additional relevant MeSH terms:
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Autoimmune Diseases
Immune System Diseases