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

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ClinicalTrials.gov Identifier: NCT02080195
Recruitment Status : Terminated (Study was unable to accrue subjects)
First Posted : March 6, 2014
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2019
Maryland Stem Cell Research Fund
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Lupus Erythematosus Graft-versus-host Disease Drug: Cyclophosphamide Drug: Fludarabine Drug: Tacrolimus Drug: Mycophenolate Mofetil Drug: Rabbit antithymocyte globulin Radiation: Total body irradiation Biological: Allogeneic bone marrow transplant Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 13, 2016
Actual Primary Completion Date : March 28, 2017
Actual Study Completion Date : March 29, 2017

Arm Intervention/treatment
Experimental: Nonmyeloablative Conditioning and BMT
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.
Drug: Cyclophosphamide
14.5 mg/kg/day on Days -6 and -5. 50 mg/kg/day on Days 3 and 4.
Other Names:
  • Cytoxan
  • Cy

Drug: Fludarabine
30 mg/m^2/day on Days -6 through -2.
Other Name: Fludara

Drug: Tacrolimus
Starting on Day 5. Dose will be adjusted according to blood levels.
Other Names:
  • FK-506
  • Prograf

Drug: Mycophenolate Mofetil
15 mg/kg three times per day from Day 5 to Day 35.
Other Names:
  • Cellcept
  • MMF

Drug: Rabbit antithymocyte globulin
0.5 mg/kg on Day -9. 2 mg/kg/day on Days -8 and -7.
Other Name: Thymoglobulin

Radiation: Total body irradiation
200 centigray on Day -1.

Biological: Allogeneic bone marrow transplant
Infusion on Day 0.
Other Name: BMT

Primary Outcome Measures :
  1. The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching [ Time Frame: 1 year ]
    Number of participants who were alive at 1 year after transplant and who had not suffered graft rejection, acute or chronic GVHD, or Grade 3 or higher (CTCAE V4.0) adverse events.

Secondary Outcome Measures :
  1. RIFLE Score [ Time Frame: 1 year ]

    Change in Responder Index for Systemic Lupus Erythematosis (RIFLE) assessment. This is a qualitative assessment of organ function. The 12 month response will be assessed as:

    complete= complete or partial resolution in more than one organ, partial= complete or partial resolution in at least one organ, the same= no change or no worsening in any organ, worse= worsening in any organ

  2. Survival [ Time Frame: 1 year ]
    Number of patients alive and alive without relapse, respectively.

  3. Graft Failure [ Time Frame: 60 days ]
    Number of participants with primary and/or secondary graft failure.

  4. Acute Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years ]
    Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

  5. Chronic Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years ]

    Percentage of participants who developed chronic GVHD as defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe).

    Mild chronic GVHD involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites).

    Moderate chronic GVHD involves 1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR 2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites).

    Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site).

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02080195

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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Maryland Stem Cell Research Fund
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Principal Investigator: Javier Bolaños-Meade, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  Study Documents (Full-Text)

Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02080195    
Other Study ID Numbers: J13134
NA_00082453 ( Other Identifier: Johns Hopkins IRB )
First Posted: March 6, 2014    Key Record Dates
Results First Posted: October 2, 2018
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Mycophenolic Acid
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents