Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)

Johns Hopkins Medicine

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Graft-versus-host Disease

Lupus Erythematosus

Treatments

Radiation: Total body irradiation

Biological: Allogeneic bone marrow transplant

Drug: Cyclophosphamide

Drug: Mycophenolate Mofetil

Drug: Tacrolimus

Drug: Rabbit antithymocyte globulin

Drug: Fludarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT02080195

J13134

NA_00082453 (Other Identifier)

Details and patient eligibility

About

The main goal of the study is to determine if bone marrow transplant (BMT) from a less specific pool of donors in combination with high dose cyclophosphamide can induce remission of refractory systemic lupus erythematosus.

Full description

Systemic lupus erythematosus (SLE) is a devastating systemic autoimmune disease that predominantly affects young women, is more common in African-Americans than in whites, and results in poor quality of life. Lupus has no cure, and up to 90% of patients require corticosteroids for disease control. More than half of patients with lupus have permanent organ damage, much of which is either directly due to or increased by corticosteroids. To satisfactorily manage moderate-to-severe SLE, the investigators need effective treatments that will allow corticosteroid-sparing.

High-dose chemotherapy followed by autologous BMT or peripheral blood progenitor transplantation (PBSCT) has been proposed as a novel approach to treat severe autoimmune diseases. Allogeneic BMT is not currently utilized for the routine treatment of SLE because of the significant morbidity (GVHD) and mortality associated with the procedure.

The investigators have recently developed an approach to BMT using post-transplant cyclophosphamide that allows us to safely perform allogeneic BMT from matched, mismatched, unrelated or haploidentical donors. Transplant-related mortality, graft-failure and risk of GVHD have been very low with this approach. Furthermore, this approach allows us to greatly expand the donor pool since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases.

This trial will employ a fludarabine + cyclophosphamide conditioning along with posttransplantation cyclophosphamide on for patients with refractory SLE. The purpose of this trial is to improve the salvage rate for patients with refractory SLE through a reformatting of the immune system.

Enrollment

1 patient

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Four or more American College of Rheumatology (ACR) criteria for the classification of SLE or 4 or more of the SLICE criteria
Involvement of one or more of the following organ systems: renal, neurologic, hematologic, cardiac, pulmonary, gastrointestinal
A lack of response to corticosteroids in moderate-to-high doses, and to either an equivalent degree of immunosuppression with azathioprine, methotrexate, cyclosporin, tacrolimus, belimumab, rituximab, mycophenolate mofetil, and/or appropriate other treatment
Patients should be eligible for transplantation according to the BMT Policy Manual

Exclusion criteria

Age less than 18 years and over 75 years
Any risk of pregnancy
Patients who are preterminal or moribund

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

1 participants in 1 patient group

Nonmyeloablative Conditioning and BMT

Experimental group

Description:

Nonmyeloablative conditioning with rabbit antithymocyte globulin, cyclophosphamide, fludarabine, and total body irradiation. Allogeneic bone marrow transplant on Day 0. Graft versus host disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and tacrolimus.

Treatment: