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

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

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: 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.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Manuela Badoglio, MS; Phone Number: +33 1 70 64 24 16; Email: manuela.badoglio@upmc.fr
• Study Contact Backup: Name: Dominique Farge, PhD; Email: dominique.farge-bancel@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Badoglio Manuela- EBMT Paris Office
    • Contact: Manuela Badoglio; Phone Number: +33.1.70.64.24.16; Email: manuela.badoglio@upmc.fr
    • Contact: Dominique Farge, PhD; Phone Number: +33 (0)1 40 27 46 13; Email: 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients treated with AHSCT for progressive systemic sclerosis in participating centres

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS),	defined as survival since AHSCT without evidence of progression of SSc.	2 years post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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	100 days post-transplant
Overall Survival (OS)	Overall survival	2 years post-transplant
Use of prednisone equivalent	Use of prednisolone equivalent > 6 mg/day for more than 3 months	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)	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)	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)	1 year and 2 years post-transplant
Infectious complications, CMV / EBV reactivation	Infectious complications, CMV / EBV reactivation	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	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.	2 years post-transplant

Collaborators and Investigators

• Sponsor: European Society for Blood and Marrow Transplantation
• Investigators: Study Chair: Dominique Farge, PhD, EBMT ADWP

Publications and helpful links

Helpful Links

• Organisation website

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 30, 2023

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Systemic sclerosis; Autoimmune diseases; Autologous hematopoietic stem cell transplant (AHSCT); Post-AHSCT management; Immune reconstitution
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: ADWP 8410025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No