Systemic lupus erythematosus (SLE) is a rare (prevalence: 40- 50/100 000 persons) heterogeneous auto-immune and auto-inflammatory disease (AD), affecting both sexes and all races, with a peak incidence / prevalence among black people and a predilection for women in the 3rd-4th decade of life. SLE is characterized by successive periods of flares and remission, which may all vary in duration and quality. Prognosis of severe forms of SLE, which affect lung, heart or brain in addition to renal involvement, has improved, but still evolution remains pejorative in a subset of patients whose 10 years mortality remains 10-15%, even in tertiary referral centers. For 20 years, no new prospective clinical trial in the course of SLE has demonstrated its effectiveness. New biological therapies have not yet made the long awaited breakthrough in the treatment of severe SLE and only anti-Blys monoclonal antibody has gained indication in moderately active SLE. In addition, serious adverse side effects (progressive multifocal leukoencephalopathy) observed with several biologics in AD patients has dampened their expected benefits. For SLE subjects resistant to 1er or 2nd line conventional treatment, there is a need to develop more effective therapies with fewer long term side effects, based on new immunomodulatory and immunosuppressive strategies. According to their in vitro immunomodulatory properties and ability to induce tissue repair mechanisms, mesenchymal stem cells (MSC) have been proposed as a new therapy for several AD, including SLE. The use of allogeneic umbilical cord-derived MSC is based on experimental and human clinical data, particularly produced by Nanjing team (Pr Sun) in China. It is also logical to select SLE patients with the same severity criteria as those used worldwide to validate the efficacy of anti-Blys therapies. Similarly, the analysis of the expected results should take into account criteria similar or comparable to those used for the pivotal clinical trials. This trial is a unique opportunity to set up collaboration between Saint-Louis APHP, clinical expert center for cell therapy in AD, and University College London for cell manufacturing.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Allogeneic Umbilical Cord derived-MSCs injected by slow intravenous infusion according to the weight of the recipient and patient groups in the study, at doses of: * 1.10\^6 CSM / kg * 2.10\^6 CSM / kg * 4.10\^6 CSM / kg 1 injection during 30min to 1h by Intravenous infusion
Saint-Louis Hospital
Paris, France
RECRUITINGToxicity of allogeneic MSC injection according to CTCAE
Immediate tolerance as assessed after the first allogeneic MSC injection, according to standards CTCAE side effects. An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3.
Time frame: 10 days
Toxicity of allogeneic MSC injection according to CTCAE Month 1
Tolerance according to side effects defined by CTCAE standards (Miller Results of cancer treatment Cancer 1981; 47 (1): 207 - 214). Treatment-related toxicity will be analyzed according to the international World Health Organization (WHO) (maximum degree of toxic attacks by the body). An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3.
Time frame: 1 month
Toxicity of allogeneic MSC injection according to CTCAE Month 3
Tolerance according to side effects defined by CTCAE standards (Miller Results of cancer treatment Cancer 1981; 47 (1): 207 - 214). Treatment-related toxicity will be analyzed according to the international World Health Organization (WHO) (maximum degree of toxic attacks by the body). An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3.
Time frame: 3 months
Toxicity of allogeneic MSC injection according to CTCAE Month 6
Tolerance according to side effects defined by CTCAE standards (Miller Results of cancer treatment Cancer 1981; 47 (1): 207 - 214). Treatment-related toxicity will be analyzed according to the international World Health Organization (WHO) (maximum degree of toxic attacks by the body). An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3.
Time frame: 6 months
Toxicity of allogeneic MSC injection according to CTCAE Month 12
Tolerance according to side effects defined by CTCAE standards (Miller Results of cancer treatment Cancer 1981; 47 (1): 207 - 214). Treatment-related toxicity will be analyzed according to the international World Health Organization (WHO) (maximum degree of toxic attacks by the body). An injection will be considered as not tolerated for any toxicity criteria above grade ≥ 3.
Time frame: 12 months
Proportion of subjects with Clinical Response Month 3
Proportion of subjects with Major Clinical Response (MCR) and the proportion of subjects with Partial Response Clinic (PCR)
Time frame: 3 months
Proportion of subjects with Clinical Response Month 6
Proportion of subjects with Major Clinical Response (MCR) and the proportion of subjects with Partial Response Clinic (PCR)
Time frame: 6 months
Proportion of subjects with Clinical Response Month 9
Proportion of subjects with Major Clinical Response (MCR) and the proportion of subjects with Partial Response Clinic (PCR)
Time frame: 9 months
Proportion of subjects with Clinical Response Month 12
Proportion of subjects with Major Clinical Response (MCR) and the proportion of subjects with Partial Response Clinic (PCR)
Time frame: 12 months
Disease activity measured by the BILAG index Month 3
Disease activity measured by the British Isles Lupus Assessment Group (BILAG) index (min=0 to max=72). The higher value is the higher is the disease activity.
Time frame: 3 months
Disease activity measured by SELENA-SLEDAI Month 3
Disease activity measured by the Safety of Estrogens in Lupus National Assessment study (SELENA) of the Systemic lupus erythematosus disease activity index (SLEDAI) (min=0 to max=105). The higher value is the higher is the disease activity.
Time frame: 3 months
Disease activity measured by SELENA-SLEDAI Month 6
Disease activity measured by the Safety of Estrogens in Lupus National Assessment study (SELENA) of the Systemic lupus erythematosus disease activity index (SLEDAI) (min=0 to max=105). The higher value is the higher is the disease activity.
Time frame: 6 months
Disease activity measured by the BILAG index Month 6
Disease activity measured by the British Isles Lupus Assessment Group (BILAG) index (min=0 to max=72). The higher value is the higher is the disease activity.
Time frame: 6 months
Disease activity measured by the BILAG index Month 9
Disease activity measured by the British Isles Lupus Assessment Group (BILAG) index (min=0 to max=72). The higher value is the higher is the disease activity.
Time frame: 9 months
Disease activity measured by SELENA-SLEDAI Month 9
Disease activity measured by the Safety of Estrogens in Lupus National Assessment study (SELENA) of the Systemic lupus erythematosus disease activity index (SLEDAI) (min=0 to max=105). The higher value is the higher is the disease activity.
Time frame: 9 months
Disease activity measured by the BILAG index Month 12
Disease activity measured by the British Isles Lupus Assessment Group (BILAG) index (min=0 to max=72). The higher value is the higher is the disease activity.
Time frame: 12 months
Disease activity measured by SELENA-SLEDAI Month 12
Disease activity measured by the Safety of Estrogens in Lupus National Assessment study (SELENA) of the Systemic lupus erythematosus disease activity index (SLEDAI) (min=0 to max=105). The higher value is the higher is the disease activity.
Time frame: 12 months
SRI Month 3
SRI (Systematic lupus erythematosus Responder Index) response rate during follow-up. A SRI response is defined as a binary outcome equal to 1 if all following conditions are validated: * 4 points reduction of SELENA SLEDAI-score * no new BILAG A score for an organ * no more than one new BILAG B score * no worsening in the overall evaluation of the physician as compared to inclusion values
Time frame: 3 months
SRI Month 6
SRI (Systematic lupus erythematosus Responder Index) response rate during follow-up. A SRI response is defined as a binary outcome equal to 1 if all following conditions are validated: * 4 points reduction of SELENA SLEDAI-score * no new BILAG A score for an organ * no more than one new BILAG B score * no worsening in the overall evaluation of the physician as compared to inclusion values
Time frame: 6 months
SRI Month 9
SRI (Systematic lupus erythematosus Responder Index) response rate during follow-up. A SRI response is defined as a binary outcome equal to 1 if all following conditions are validated: * 4 points reduction of SELENA SLEDAI-score * no new BILAG A score for an organ * no more than one new BILAG B score * no worsening in the overall evaluation of the physician as compared to inclusion values
Time frame: 9 months
SRI Month 12
SRI (Systematic lupus erythematosus Responder Index) response rate during follow-up. A SRI response is defined as a binary outcome equal to 1 if all following conditions are validated: * 4 points reduction of SELENA SLEDAI-score * no new BILAG A score for an organ * no more than one new BILAG B score * no worsening in the overall evaluation of the physician as compared to inclusion values
Time frame: 12 months
comorbidities Month 3
Presence of comorbidities
Time frame: 3 months
comorbidities Month 6
Presence of comorbidities
Time frame: 6 months
comorbidities Month 9
Presence of comorbidities
Time frame: 9 months
comorbidities Month 12
Presence of comorbidities
Time frame: 12 months
Quality of life Month SF-36 Month 3
Quality of life assessed by the Short Form 36 version 2 (SF-36v2). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 3 months
Quality of life EQ-5D Month 3
EuroQol-5D (EQ-5D) : health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated from 0 to 5 and a single summary index is obtained by summing all the dimensions (min=0 to max=25).
Time frame: 3 months
Quality of life Month SF-36 Month 6
Quality of life assessed by the Short Form 36 version 2 (SF-36v2). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 6 months
Quality of life EQ-5D Month 6
EuroQol-5D (EQ-5D) : health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated from 0 to 5 and a single summary index is obtained by summing all the dimensions (min=0 to max=25).
Time frame: 6 months
Quality of life Month SF-36 Month 9
Quality of life assessed by the Short Form 36 version 2 (SF-36v2). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 9 months
Quality of life EQ-5D Month 9
EuroQol-5D (EQ-5D) : health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated from 0 to 5 and a single summary index is obtained by summing all the dimensions (min=0 to max=25).
Time frame: 9 months
Quality of life Month SF-36 Month 12
Quality of life assessed by the Short Form 36 version 2 (SF-36v2). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 12 months
Quality of life EQ-5D Month 12
EuroQol-5D (EQ-5D) : health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated from 0 to 5 and a single summary index is obtained by summing all the dimensions (min=0 to max=25).
Time frame: 12 months
Steroids Month 3
Percentage of subjects with an average dose of prednisone reduced by 25% compared to M0
Time frame: 3 months
Steroids Month 6
Percentage of subjects with an average dose of prednisone reduced by 25% compared to M0
Time frame: 6 months
Steroids Month 9
Percentage of subjects with an average dose of prednisone reduced by 25% compared to M0
Time frame: 9 months
Steroids Month 12
Percentage of subjects with an average dose of prednisone reduced by 25% compared to M0
Time frame: 12 months
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