Clinical trial NCT02080195: Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)
Official title: A Phase I/II Study of Nonmyeloablative Conditioning and Transplantation of Human Leukocyte Antigen (HLA)-Matched, Partially HLA-mismatched, HLA-haploidentical or Matched Unrelated Bone Marrow for Patients With Refractory SLE
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lupus Erythematosus
Graft-versus-host Disease
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Maryland Stem Cell Research Fund
First posted: 2014-03-06
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching
timeFrame: 1 year
Secondary outcomes:
measure: RIFLE Score
timeFrame: 1 year
measure: Survival
timeFrame: 1 year
measure: Graft Failure
timeFrame: 60 days
measure: Acute Graft Versus Host Disease (GVHD)
timeFrame: Up to 2 years
measure: Chronic Graft Versus Host Disease (GVHD)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Javier Bolaños-Meade, MD
role: PRINCIPAL_INVESTIGATOR
References: