Sirolimus for Autoimmune Disease of Blood Cells

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Treatment for patients with autoimmune destruction of blood cells is poor. The part of the body that fights infections is called the immune system and white blood cells (WBCs) are part of the immune system. Normally, a person's body creates WBCs to fight infections and eliminates WBCs which have stopped helping the body function. Patients with autoimmune destruction of blood cells have difficulty eliminating old WBCs. The abnormal WBCs build up and can damage other healthy cells, which can lead to anemia, fatigue, jaundice, internal bleeding, infection, and cancer. Few effective medications exist for treatment for patients with autoimmune cytopenias and those commonly used are fraught with side effects. Nevertheless, as scientific understanding of autoimmune diseases has improved, more directed and less toxic therapies are becoming available. A number of groups have been studying the efficacy of a medication called sirolimus in patients with autoimmune diseases. This medicine has been FDA-approved for over 20 years. Sirolimus is a medicine used in children with other diseases. Sirolimus works, in part, by eliminating old and abnormal WBCs. Our group and others have shown that sirolimus is effective in mice with autoimmunity and in children with a rare condition called Autoimmune Lymphoproliferative Syndrome (ALPS). We believe sirolimus will help children with autoimmune cytopenias. We believe it will improve their symptoms and make them less sick. We propose to study sirolimus in children with chronic and/or refractory autoimmune cytopenias.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• Age > 12 months and < 30 years at the time of study entry

• Diagnosis of autoimmune cytopenias requiring treatment with medications

• At least one of the following: Autoimmune Neutropenia, Autoimmune Hemolytic Anemia, and/or Autoimmune Thrombocytopenia

• Must be proven autoimmune by either a documented autoantibody (positive direct anti globulin test, positive anti-neutrophil, and/or anti-platelet antibody) and/or a documented clinical response to immunosuppression

• Autoimmune Cytopenias can be idiopathic (Idiopathic Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Autoimmune Neutropenia (AIN), or Evans syndrome) or secondary to one of following conditions: Lupus, Rheumatoid Arthritis (RA), ALPS (Autoimmune Lymphoproliferative Syndrome), or Inflammatory bowel disease (IBD)

• Patients must have chronic disease diagnosed by either a documented cytopenia syndrome (Lupus, ALPS, RA, or IBD), or by having Evans syndrome defined as idiopathic destruction of multiple blood cell types, and/or by having disease >6 months

• Patients must be refractory to or unable to tolerate standard front-line therapies for autoimmune cytopenias (corticosteroids and/or IVIG)

• Patients may be taking second-line agents for autoimmune cytopenias (mycophenolate mofetil, cyclosporine, tacrolimus, mercaptopurine, and/or methotrexate) at time of study entry; however, attempts should be made to wean these agents. Patients may not stay on a combination of sirolimus and a calcineurin inhibitor for greater than 4 weeks

• Informed consent/assent must be obtained prior to initiating treatment

• Patient must be able to consume oral medication in the form of tablets or solution

Exclusion Criteria:

• Pregnancy or breast feeding

• Uncontrolled infection

• Known allergy to Sirolimus or its components

• Patients with a documented malignancy on therapy or not in remission

• Patients who do not meet organ function requirements listed in protocol

• Patients with a documented history of severe combined immunodeficiency or human immunodeficiency virus infection (HIV)