Autologous Stem Cell Transplantation: International Lupus Trial

• Status: Withdrawn
• Trial end date: 2017-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate remission induction therapy for refractory Lupus Erythematosus with autologous hematopoietic stem cell transplantation (AHSCT) versus Rituximab (anti CD20) followed by maintenance therapy with mycophenolate mofetil (MMF).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Society for Blood and Marrow Transplantation
• Collaborator: EULAR
• Treatments: Mycophenolic Acid; Rituximab

Criteria

Inclusion Criteria:

1. Age between 16 and 60 years.

2. Diagnosis of systemic lupus erythematosus (SLE) according to ACR-criteria with antinuclear antibodies positive (ANA) on at least 2 successive tests at 3 months interval plus disease duration of more than 5 years since the diagnosis or first time of intensive immunosuppressive drugs.

3. Sustained or relapsed active BILAG A SLE with documented evidence of at least one visceral involvement or refractory SLE as defined by either:

• kidney involvement: with the criteria for lupus renal BILAG A and a creatinine clearance > 30 ml/min/m2, not explained by other causes than SLE activity with a renal biopsy of less than 12 months showing a class III or IV lupus nephritis

• Any other type of vital organ involvement except mesenteric vasculitis with BILAG neurologic category A, cardiovascular or pulmonary category A, vasculitis category A

• Auto-immune cytopenias (hemolytic anemia and/or thrombo-cytopenia) defined as BILAG hematologic category A and confirmed by a bone marrow aspirate

• Secondary antiphospholipid syndrome (SAPL) active despite full (INR > 3) anticoagulation after at least 6 months of the best standard local therapy using CY or MMF either alone or successively according to:

• the short term Eurolupus protocol low dose CY regimen of 6 x 500 mg iv CY at 2 weeks interval or

• the conventional treatment with 0.75 g/m2/month x 6 iv cyclophosphamide or

• MMF at 2 g daily for 3 to 6 months plus oral steroids above 0.5 mg/kg/day and be corticosteroids dependent and unable to decrease below 20 mg/day.

4. Negative pregnancy test for women of child bearing age.

5. Written informed consent.

Exclusion Criteria:

1. Pregnancy, breast feeding or unwillingness to use adequate contraception methods during study (see 7.5).

2. Severe concomitant disease:

• Respiratory: mean PAP > 50 mmHg (by cardiac echo or right heart catheterization), DLCO < 40% predicted, respiratory failure as defined by a resting arterial oxygen tension (PaO2) < 70 mmHg) and/or resting arterial carbon dioxide tension (PaCO2)> 50 mmHg) without oxygen supply

• Renal: creatinine clearance < 30 ml/min

• Cardiac: clinical evidence of congestive heart failure; LVEF < 40% (cardiac echo or multigated radionuclide angiography (MUGA)); > 1 cm pericardial effusion on cardiac echography; uncontrolled ventricular arrhythmia.

3. Liver failure defined as a transaminases levels (ASAT, ALAT > 2 normal) unless related to activity of the disease.

4. Severe psychiatric disorders, including severe psychosis related to SLE disease that may prevent the ability to sign informed consent or undergo the procedure.

5. Concurrent neoplasms or myelodysplasia except for localized basal cell carcinoma or squamous skin cancer or in situ cervical carcinoma of the uterus.

6. Bone marrow insufficiency defined as neutropenia < 0.5 x 109/l, thrombo- cytopenia < 30 x 109/l, anaemia < 8 g/dl, CD4+ T lymphopenia < 200 x 106/l.

7. Uncontrolled acute or chronic infection, including HIV, HTLV-1, 2 positivity, Hepatitis B surface Ag positive, hepatitis C PCR positive.

8. Previous treatments with TLI, TBI or alkylating agents including cyclophosphamide > 15 g cumulative.

9. Intracranial hematoma or previous bleeding documented within 30 days of the screening visit.

10. Mesenteric vasculitis or ongoing gastrointestinal bleeding.

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