Phase I Study of Immune Ablation and CD34+ Peripheral Blood Stem Cell Support in Patients With Systemic Lupus Erythematosus

Sponsor

Northwestern Memorial Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00017641

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

OBJECTIVES:

Determine the safety of immune ablation with high-dose cyclophosphamide and anti-thymocyte globulin followed by peripheral blood stem cell support in patients with systemic lupus erythematosus.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: filgrastim Procedure: CD34+ Peripheral Blood Stem Cell Reinfusion	Phase 1

Detailed Description

PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1 hour for 2 doses. Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 24 hours after completion of cyclophosphamide and continuing until leukapheresis is complete. Leukapheresis continues daily until target number of cells is harvested. CD 34+ cells are isolated from peripheral blood stem cells (PBSC) in vitro.

Patients then receive cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV over 10 hours on days -4 to -2, and G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients undergo reinfusion of CD34+ PBSC on day 0.

Patients are followed weekly for 90 days, monthly for 1 year, and at 2 years.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Study Start Date :

Apr 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of systemic lupus erythematosus with 1 of the following malignant features:

Nephritis (WHO class III or IV)
Failed NIH short-course cyclophosphamide therapy
Vasculitis/immune complex deposition causing end organ signs or symptoms (e.g., cerebritis, transverse myelitis, pulmonary hemorrhage, cardiac failure, or renal failure)
Hematologic cytopenias that are immune mediated and uncontrolled by conservative measures with any of the following:

Transfusion-dependent anemia with untransfused hemoglobin less than 8 g/dL

Platelet count less than 40,000/mm3 (without transfusions)

Granulocyte count less than 1,000/mm3

Catastrophic anti-phospholipid syndrome

--Patient Characteristics--

Cardiovascular:

LVEF at least 35%
No lupus-induced myocarditis
No history of unstable angina

Pulmonary:

FEV1/FVC at least 50% predicted
DLCO at least 50% predicted

Other:

HIV negative
No prior or concurrent malignancy except localized basal cell or squamous cell skin cancer
No uncontrolled diabetes mellitus
No medical illness that would preclude study
No psychiatric illness or mental deficiency that would preclude study
No known hypersensitivity to E. coli-derived proteins
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception