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SNCTP000004441 | NCT04464434 | BASEC2020-03038

Autologe Stammzelltransplantation bei Patienten mit Systemsklerose: Erstlinientherapie oder letzter Ausweg?

Data source: BASEC (Imported from 21.06.2021), WHO (Imported from 18.04.2021)
Changed: 04.06.2021
Disease category: Skin and Connective Tissues diseases (non cancer)

Brief description of trial (Data source: BASEC)

Die Systemsklerose ist eine seltene systemische Autoimmunerkrankung, die mit Hautstraffung, Entzündung und einer lebensbedrohlichen Schädigung der inneren Organe einhergehen kann.

Es gibt verschiedene Behandlungen für schwere Formen der Systemsklerose. Autologe Stammzelltransplantation (SZT), Chemotherapie und Immunsuppressiva werden in der gegenwärtigen Praxis verwendet, um das Fortschreiten der Krankheit zu hemmen.
Die optimale Behandlungsstrategie und das beste Timing der SCT bei schweren Formen der Systemsklerose sind jedoch unbekannt.

Mit der UPSIDE-Studie vergleichen wir bei Patienten mit schwerer Systemsklerose zwei Behandlungsstrategien.
Die erste Strategie besteht aus dem sofortigen Einsatz der SZT.
Bei der zweiten Strategie soll zuerst die herkömmliche immunsuppressive Behandlung eingesetzt werden (Chemotherapie gefolgt von dem Medikament Mycophenolatmofetil) und eine SZT erst dann zur Anwendung kommen, wenn die herkömmliche immunsuppressive Behandlung versagen sollte..

Diese Forschung wurde von der UMC Utrecht in den Niederlanden durchgeführt und wird von Rheumatologen in verschiedenen Zentren in Europa durchgeführt. 120 Patienten mit dcSSc werden an dieser Studie teilnehmen. Die Studiendauer beträgt mindestens fünf Jahre. Durch die Auslosung wird festgelegt, welcher Behandlungsstrategie jeder Teilnehmer zugeteilt wird.

Für diese Studie suchen wir erwachsene Patienten mit schwerer Systemsklerose, wobei die Erst-manifestation der Erkrankung nicht länger als zwei Jahre zurück liegt. Der sogenannte „Haut-Score (mRSS)“ soll hierbei mehr als 15 betragen oder es muss eine Beteiligung bestimmter innerer Organe vorliegen..

Bevor Patienten an dieser Studie teilnehmen können, wird festgestellt, ob die in der Studie angegebenen Behandlungen sicher durchgeführt werden können. Diese Untersuchungen beinhalten Blut- und Urintests, eine Lungenfunktionsuntersuchung, Ultraschall des Herzens, Messung des Blutdruckes im Lungenkreislauf mittels Katheterunters und ein 24-Stunden-EKG.

Health conditions investigated (Data source: BASEC)

systemischer sklerose

Health conditions (Data source: WHO)

Systemic Sclerosis;Systemic Scleroses, Diffuse;Scleroderma;Scleroderma, Diffuse;Autologous Stem Cell Transplantation;Cyclophosphamide;Mycophenolate Mofetil;Treatment Strategy

Rare disease (Data source: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Mit der UPSIDE-Studie vergleichen wir bei Patienten mit schwerer Systemsklerose zwei Behandlungsstrategien.
Die erste Strategie besteht aus dem sofortigen Einsatz der SZT.
Bei der zweiten Strategie soll zuerst die herkömmliche immunsuppressive Behandlung eingesetzt werden (Chemotherapie gefolgt von dem Medikament Mycophenolatmofetil) und eine SZT erst dann zur Anwendung kommen, wenn die herkömmliche immunsuppressive Behandlung versagen sollte.

Interventions (Data source: WHO)

Procedure: Upfront autologous HSCT

Criteria for participation in trial (Data source: BASEC)

- Patienten im Alter von 18 bis 65 Jahren
- Diagnose: Diffuse kutane Systemsklerose
- Krankheitsdauer ≤ 2 Jahre und mRSS ≥ 15 und/oder Organbeteiligung (Lungen, Nieren oder Herz)

Exclusion criteria (Data source: BASEC)

- Schwangerschaft
- Schwerwiegende gesundheitliche Probleme
- Vorherige Behandlung mit Cyclophosphamid (einem bestimmten Immunsuppressivum)

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

1. Age between 18 and 65 years.

2. Fulfilling the 2013 ACR-EULAR classification criteria for SSc (appendix B).

3. Disease duration = 2 years (from onset of first non-Raynaud's symptoms) and diffuse
cutaneous disease with

- mRSS = 15 and/or

- clinically significant organ involvement as defined by either:

1. respiratory involvement = i. DLCO and/or (F)VC = 85% (of predicted) and
evidence of interstitial lung disease on HR-CT scan with clinically relevant
obstructive disease and emphysema excluded.

ii. Patients with a DCLO and/or FVC > 85%, but with a progressive course of
lung disease: defined as relative decline of >10% in FVC predicted and/or
TLC predicted, or >15% in DLCO predicted and evidence of interstitial lung
disease on HR-CT scan with clinically relevant obstructive disease and
emphysema excluded, within 12 months. Intercurrent infections excluded.

2. renal involvement = any of the following criteria: hypertension (two
successive BP readings of either systolic = 160 mm Hg or diastolic > 110 mm
Hg, at least 12 hours apart), persistent urinalysis abnormalities
(proteinuria, haematuria, casts), microangiopathic haemolytic anaemia, new
renal insufficiency (serum creatinine > upper limit of normal);
non-scleroderma related causes (e.g. medication, infection etc.) must be
reasonably excluded.

3. cardiac involvement = any of the following criteria: reversible congestive
heart failure, atrial or ventricular rhythm disturbances such as atrial
fibrillation or flutter, atrial paroxysmal tachycardia or ventricular
tachycardia, 2nd or 3rd degree AV block, pericardial effusion (not leading
to hemodynamic problems), myocardi-tis; non-scleroderma related causes must
have been reasonably excluded.

4. Written Informed consent

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during study

2. Concomitant severe disease =

1. respiratory: resting mean pulmonary artery pressure (mPAP) > 20 mmHg (by right
heart catheterisation), DLCO < 40% predicted, respiratory failure as defined by
the primary endpoint

2. renal: creatinine clearance < 40 ml/min (measured or estimated)

3. cardiac: clinical evidence of refractory congestive heart failure; LVEF < 45% by
cardiac echo or cardiac MR; chronic atrial fibrillation necessitating oral
anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with
hemodynamic consequences

4. liver failure as defined by a sustained 3-fold increase in serum transaminase or
bilirubin, or a Child-Pugh score C

5. psychiatric disorders including active drug or alcohol abuse

6. concurrent neoplasms or myelodysplasia

7. bone marrow insufficiency defined as leukocytopenia < 4.0 x 109/L,
thrombocytopenia < 50x 10^9/L, anaemia < 8 gr/dL, CD4+ T lymphopenia < 200 x
106/L

8. uncontrolled hypertension

9. uncontrolled acute or chronic infection, including HIV, HTLV-1,2 positivity

10. ZUBROD-ECOG-WHO Performance Status Scale > 2

3. Previous treatments with immunosuppressants > 6 months including MMF, methotrexate,
azathioprine, rituximab, tocilizumab, glucocorticosteroids.

4. Previous treatments with TLI, TBI or alkylating agents including CYC.

5. Significant exposure to bleomycin, tainted rapeseed oil, vinyl chloride,
trichlorethylene or silica;

6. eosinophilic myalgia syndrome; eosinophilic fasciitis.

7. Poor compliance of the patient as assessed by the referring physicians.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT04464434

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT04464434

Further information on trial

Date trial registered

25.06.2020

Incorporation of the first participant

17.09.2020

Recruitment status

Recruiting

Academic title (Data source: WHO)

Upfront Autologous Hematopoietic Stem Cell Transplantation Versus Immunosuppressive Medication in Early Diffuse Cutaneous Systemic Sclerosis: an International Multicentre, Open-label, Randomized Con-trolled Trial

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Number of patients who survive without major events (event free survival)

Secundary end point (Data source: WHO)

Changes in handmobility;Changes in fatigue measured with the FACIT questionnaire;Changes in ability to work, measured by the customized Productivity Cost Questionnaire (iPCQ);Changes in daily functioning;Changes in sexual functioning;Inflammatory and fibrotic characteristics and changes of the skin and composition of the microbiome of the skin;Changes in self-assessed skin thickness (PASTUL_);Changes in several subsets of the immune system;Changes in gastrointestinal complaints (UCLA SCTC GIT 2.0);Changes in 18F FDG-PET scan from the thorax;Changes in nailfold capillaroscopy;Changes in health related quality of life EQ-5D-5L index;Changes in pulmonary function;Changes in cardiac function(Left Ventricular Ejection Fraction);Changes in skin involvement (modified Rodnan Skin Score);The area under the curve (AUC) of the CRISS over time;Number of CTCAE toxicity advserse events;Number of patient alive after 24 months (Overall mortality);Number of patients who die due to complications related to the treatment (Treatment related mortality);Number of patients who survive without disease progression (Progression-free survival)

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Basel

Countries (Data source: WHO)

Belgium, Croatia, Germany, Italy, Netherlands, Sweden, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Prof. dr. U. Walker
0000000000000
Ulrich.Walker@usb.ch

Contact for general information (Data source: WHO)

Jacob M van Laar, MD PhD;Julia Spierings;Julia Spierings, MD
UMC Utrecht
+31641888582
J.Spierings@umcutrecht.nl

Contact for scientific information (Data source: WHO)

Jacob M van Laar, MD PhD;Julia Spierings;Julia Spierings, MD
UMC Utrecht
+31641888582
J.Spierings@umcutrecht.nl

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

UMC Utrecht

Additional sponsors (Data source: WHO)

ZonMw: The Netherlands Organisation for Health Research and Development;Boehringer Ingelheim;Miltenyi Biotec, Inc.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Date of authorisation by the ethics committee

04.06.2021

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2020-03038

Secondary ID (Data source: WHO)

NL72607.041.20