Reduced Intensity Transplant in Medically Refractory Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc)

Study Overview
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Brief Summary
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The purpose of this study is to determine if a reduced intensity (RI) (non-myeloablative) chemoimmunotherapy followed by Allogeneic Stem Cell Transplantation AlloSCT (matched family donors and matched unrelated cord blood donors) will be well tolerated.

Detailed Description
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This is to test whether a reduced intensity will result in a high degree of mixed or complete donor chimerism and stabilization of autoimmune disease in a select group of patients with medically refractory SLE or SSc.

Official Title
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Reduced Intensity Conditioning And Allogeneic Stem Cell Transplantation in Patients With Medically Refractory Systemic Lupus Erythematosus and Medically Refractory Systemic Sclerosis (SSc)

Conditions
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Systemic Lupus Erythematosus, Systemic Sclerosis

Intervention / Treatment
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* Procedure: Reduced Intensity Allogeneic Transplant
* Drug: Fludarabine
* Drug: Busulfan
* Drug: Campath


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diffuse Systemic Sclerosis and variants as per ACR criteria Medically refractory disease Adequate Organ Function - Pulmonary function Renal function, Cardiac function defined as: SGOT (AST) or SGPT (ALT) <5 x upper limit of normal Diagnosis of SLE - Medically refractory disease Exclusion Criteria: Karnofsky/Lansky <60%

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Intensity Regimen for Refractory SLE<br>RI regimen of fludarabine/busulfan and Alemtuzumab (FBA) followed by AlloSCT in selected patients with medically refractory Systemic Lupus Erythematosus (SLE). | Procedure: Reduced Intensity Allogeneic Transplant<br>* Eeduced intensity allogeneic stem cell transplantation with a fludarabine/busulfan/alemtuzumab conditioning regimen is anticipated to result in mixed and/or complete donor chimerism and potentially alter the natural history and outcome of patients with medically refractory Systemic Lupus Erythematosus (SLE) or Systemic Sclerosis (SSc).<br>Drug: Fludarabine<br>* Fludarabine 30 mg/m2 Day -7, -6, -5, -4, -3, -2<br>Drug: Busulfan<br>* Busulfan 3.2 mg/kg Days _8, -7, -6, -5<br>Drug: Campath<br>* Campath: 2 mg/m2 Day -5; 6 mg/m2 Day -4, -3; 20 mg/m2 Day -2<br>* Other names: Alemtuzumab;|
| Experimental: Reduced Intensity Regimen for SSc<br>RI regimen of fludarabine/busulfan and Alemtuzumab (FBA) followed by AlloSCT in selected patients with Systemic Sclerosis (SSc). | Procedure: Reduced Intensity Allogeneic Transplant<br>* Eeduced intensity allogeneic stem cell transplantation with a fludarabine/busulfan/alemtuzumab conditioning regimen is anticipated to result in mixed and/or complete donor chimerism and potentially alter the natural history and outcome of patients with medically refractory Systemic Lupus Erythematosus (SLE) or Systemic Sclerosis (SSc).<br>Drug: Fludarabine<br>* Fludarabine 30 mg/m2 Day -7, -6, -5, -4, -3, -2<br>Drug: Busulfan<br>* Busulfan 3.2 mg/kg Days _8, -7, -6, -5<br>Drug: Campath<br>* Campath: 2 mg/m2 Day -5; 6 mg/m2 Day -4, -3; 20 mg/m2 Day -2<br>* Other names: Alemtuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Toxicity associated with reduced intensity regimen of fludarabine/busulfan and Campath followed by allogeneic stem cell transplant in patients with medically refractory Systemic Lupus Erythematosus (SLE) or SSc is measured. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chimerism | Percentage(%) of mixed and/or complete donor chimerism has been measured at different time points. | 1 year | 
| Immune Reconstitution. | Peripheral blood for immune reconstitution for T-cell, B-cell and NK cells to be obtained for measurement of cell. | 1 year | 
| Progression Free and Overall Survival. | Probability of progression free and overall survival will be measured. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Disease, Reduced Intensity Transplant