Clinical trial NCT01895244: Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis
Official title: Highdose Chemotherapy and Transplantation of 34+ Selected Stem Cell for Progressive Systemic Sclerosis - Modification According to Manifestation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Scleroderma
Cardiac Involvement
Autologous Stem Cell Transplantation
Keywords: scleroderma
autologous stem cell transplantation
thiotepa
cluster of differentiation (CD) 34 selection
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Autologous stem cell therapy has been shown to be effective in patients with systemic sclerosis. Nevertheless treatment is associated with treatment related mortality and patients die during follow up despite successful transplantation.

Intention of this trial is to improve overall survival by modifying the existing protocol used for the ASTIS trial.

To reduce treatment toxicity we reduce the dose of Cyclophosphamide (CYC) for mobilisation to 2x1g.

Especially in patients with cardiac manifestations we also modify the conditioning regimen by adding thiotepa and reducing CYC; as CYC has known cardiotoxic side effects.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of progressive systemic sclerosis \<7 years
* Progressive course despite cyclophosphamide pretreatment
* Cyclophosphamide i.v.: at least 3 x with 500-1000 mg/m² every 3-4 weeks or
* Cyclophosphamide p.o. with at least 100mg/day for at least 2 months or
* Contraindication to treatment with cyclophosphamide
* Progress defined as at least one of the following criteria:

  * Increase in the mRSS
  * Worsening of the lung function
  * Increase in fibrosis/alveolitis in thorax CT
  * Worsening kidney function through manifestation of systemic sclerosis
* Limited or diffuse cutaneous progressive form of Ssc with organ manifestation in the lungs/heart or kidneys

Exclusion Criteria:

* Age \<18 years
* Pregnancy or inadequate contraception
* Severe heart failure with ejection fraction (EF) \< 30% in echo
* Pulmonary arterial hypertension with systolic pulmonary arterial pressure (PAPsys) \>50mm Hg
* Kidney insufficiency: creatinine clearance \<30 ml/min
* Reduced lung function
* Inspiratory vital capacity (IVC) \< 50% of normal
* Carbon monoxide (CO)-Diffusion capacity SB \< 40%
* Previously damaged bone marrow
* Leukopenia \< 2,000/µl
* Thrombopenia \< 100,000/µl
* Previous myelotoxic treatment:
* Cyclophosphamide \> 50g cumulative (relative)
* Infection (Hepatitis B/C, HIV, Salmonella carrier, syphilis, relative: history of tuberculosis)
* Severe concomitant psychiatric illness (depression, psychosis)
* Substance dependence
* Continued nicotine abuse
* Continued alcohol abuse
* Continued drug abuse
* Consent not given
* Poor compliance

Primary outcomes:
measure: Efficay - Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: Safety - Treatment related mortality
timeFrame: 100 days
measure: Time to engraftment
timeFrame: 2 months
measure: Progression free survival
timeFrame: 3 years
measure: Efficacy - Lung function test and Skin
timeFrame: 3 years
Other outcomes:
measure: Efficacy - Patient reported outcome
timeFrame: 3 years
Locations:
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology
Study officials:
affiliation: University Hospital Tuebingen, Department of oncology, hematology, rheumatology
name: Joerg C Henes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henes JC, Koetter I, Horger M, Schmalzing M, Mueller K, Eick C, Bauer A, Vogel W, Kanz L. Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations. Rheumatology (Oxford). 2014 May;53(5):919-22. doi: 10.1093/rheumatology/ket464. Epub 2014 Jan 22.