Autologous Stem Cell Transplantation: International Lupus Trial

NCT05063513 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2008-ADWP-01EUdraCT No: 2008-006090-32
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS

Keywords

Lupus; Transplant; Rituximab; Mycophenolate Mofetil; Autologous Hematopoietic Stem Cell Transplantation; Refractory Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• To compare the efficacy of Autologous Hematopoietic Stem Cell Transplantation (study arm) versus rituximab (control arm), followed by maintenance therapy with Mycophenolate Mofetil for patients with severe Systemic Lupus Erythematosus

  The proportion of patients who achieve clinical success defined by combined renal and extra renal remission with independence from all other immunosuppressive agents other than MMF

  2 years

Secondary Outcomes (6)

• Treatment completion

  5 years

• Clinical success

  5 years

• Disease activity

  5 years

• Disease damage

  5 years

• Quality of Life

  5 years

Study Arms (2)

Transplant arm

EXPERIMENTAL

Experimental arm will undergo mobilisation with cyclophosphamide (CY) 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.

Biological: Autologous Hematopoietic Stem Cell Transplantation

Rituximab arm

ACTIVE COMPARATOR

Control arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.

Drug: Rituximab

Interventions

Autologous Hematopoietic Stem Cell Transplantation BIOLOGICAL

Experimental arm will undergo mobilisation with CY 4 g/m2 (in two divided doses), followed by Autologous Hematopoietic Stem Cell Transplantation using CY (200 mg/kg body weight given in 4 daily doses) plus ATG and unmanipulated autologous graft and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.

Also known as: Cellcept for Mycophenolate Mofetil

Transplant arm

Rituximab DRUG

Control arm will receive 4 successive weekly infusions of rituximab (antiCD20) 375 mg/m2 body surface area for four weeks and maintenance by Mycophenolate Mofetil (2 g/day) starting 3 months after randomization.

Also known as: MabThera for Rituximab, Cellcept for Mycophenolate Mofetil

Rituximab arm

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 16 and 60 years.
• 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.
• 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.
• Negative pregnancy test for women of child bearing age.
• Written informed consent.

You may not qualify if:

• Pregnancy, breast feeding or unwillingness to use adequate contraception methods during study (see 7.5).
• 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.
• Liver failure defined as a transaminases levels (ASAT, ALAT \> 2 normal) unless related to activity of the disease.
• Severe psychiatric disorders, including severe psychosis related to SLE disease that may prevent the ability to sign informed consent or undergo the procedure.
• Concurrent neoplasms or myelodysplasia except for localized basal cell carcinoma or squamous skin cancer or in situ cervical carcinoma of the uterus.
• 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.
• Uncontrolled acute or chronic infection, including HIV, HTLV-1, 2 positivity, Hepatitis B surface Ag positive, hepatitis C PCR positive.
• Previous treatments with TLI, TBI or alkylating agents including cyclophosphamide \> 15 g cumulative.
• Intracranial hematoma or previous bleeding documented within 30 days of the screening visit.
• Mesenteric vasculitis or ongoing gastrointestinal bleeding.
• Poor compliance of the patient as assessed by the referring physicians.

Sponsors & Collaborators

• European Society for Blood and Marrow Transplantation: lead
• EULAR: collaborator

Study Sites (1)

Dept. of Internal Medicine, Hôpital Saint-Louis

Paris, F-75475, France

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Mycophenolic Acid; Rituximab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dominique Farge, MD

  Dept. of Internal Medicine, Hôpital Saint-Louis, 1 Avenue ClaudeVellefaux, F-75475ParisCédex 10, France.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2009
• First Posted: October 1, 2021
• Study Start: July 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2017
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

FR (1)